Search

Your search keyword '"Lendemeijer B"' showing total 34 results
Start Over Author "Lendemeijer B"
34 results on '"Lendemeijer B"'

1. Rapid specification of human pluripotent stem cells to functional astrocytes

Author

Lendemeijer, B., primary, Unkel, M., additional, Mossink, B., additional, Hijazi, S., additional, Sampedro, S.G., additional, Shpak, G., additional, Slump, D.E., additional, van den Hout, M.C.G.N., additional, van IJcken, W.F.J., additional, Bindels, E.M.J., additional, Hoogendijk, W.J.G., additional, Nadif Kasri, N., additional, de Vrij, F.M.S., additional, and Kushner, S.A., additional

Published
2022
Full Text
View/download PDF

4. Poster abstracts

Author

Ferrie, J., Shipley, M., Cappuccio, F., Brunner, E., Miller, M., Kumari, M., Marmot, M., Coenen, A., Castillo, J. L., Araya, F., Bustamante, G., Montecino, L., Torres, C., Oporto, S., Gronli, J., Fiske, E., Murison, R., Bjorvatn, B., Sorensen, E., Ursin, R., Portas, C. M., Rajaraman, S., Gribok, A., Wesensten, N., Balkin, T., Reifman, J., Dursunoglu, N., Ozkurt, S., Baser, S., Delen, O., Sarikaya, S., Sadler, P., Mitchell, P., Françon, D., Decobert, M., Herve, B., Richard, A., Griebel, G., Avenet, P., Scatton, B., Fur, G. L., Eckert, D., Jordan, A., Wellman, A., Smith, S., Malhotra, A., White, D., Bruck, D., Thomas, I., Kritikos, A., Oertel, W., Stiasny-Kolster, K., Garcia-Borreguero, D., Poewe, W., Hoegl, B., Kohnen, R., Schollmayer, E., Keffel, J., Trenkwalder, C., Valle, A., Roizenblatt, S., Fregni, F., Boggio, P., Tufik, S., Ward, K., Robertson, L., Palmer, L., Eastwood, P., Hillman, D., Lee, J., Mukherjee, S., de Padova, V., Barbato, G., Ficca, G., Zilli, I., Salzarulo, P., Veldi, M., Hion, T., Vasar, V., Kull, M., Nowak, L., Davis, J., Latzer, Y., Tzischinsky, O., Crowley, S., Carskadon, M., Anca-Herschkovitsch, M., Frey, D., Ortega, J., Wiseman, C., Farley, C., Wright, K., Campbell, A., Neill, A., Spiegel, K., Leproult, R., Tasali, E., Scherberg, N., van Cauter, E., Noradina, A. T., Karim, N. A., Norlinah, I., Raymond, A. A., Sahathevan, R., Hamidon, B., Werth, E., Poryazova, R., Khatami, R., Bassetti, C., Beran, R. G., Ainley, L., Holand, G., Duncan, J., Kinney, H., Davis, B., Hood, B., Frey, S., Schmidt, C., Hofstetter, M., Peigneux, P., Cajochen, C., Hu, W.-P., Li, J.-D., Zhang, C., Boehmer, L., Siegel, J., Zhou, Q.-Y., Sagawa, Y., Kondo, H., Takemura, T., Kanayama, H., Kaneko, Y., Sato, M., Kanbayashi, T., Hishikawa, Y., Shimizu, T., Viola, A., James, L., Schlangen, L., Dijk, D.-J., Andretic, R., Kim, Y.-C., Han, K.-A., Jones, F., Greenspan, R., Sanford, L., Yang, L., Tang, X., Dieter, K., Uta, E., Sven, H., Richard, M., Oyane, N., Pallesen, S., Holsten, F., Inoue, Y., Fujita, M., Emura, N., Kuroda, K., Uchimura, N., Johnston, A., Astbury, J., Kennedy, G., Hoedlmoser, K., Schabus, M., Pecherstorfer, T., Moser, S., Gruber, G., Anderer, P., Klimesch, W., Naidoo, N., Ferber, M., Pack, A., Neu, D., Mairesse, O., Hoffmann, G., Dris, A., Lambrecht, L., Linkowski, P., Verbanck, P., Le Bon, O., Matsuura, N., Yamao, M., Adachi, N., Aritomi, R., Komada, Y., Tanaka, H., Shirakawa, S., Kondoh, H., Takemura, F., Ohnuma, S., Suzuki, M., Uemura, S., Iskra-Golec, I., Smith, L., Thanh, D.-V., Boly, M., Phillips, C., Steven, L., Luxen, A., Maquet, M., Jay, S., Dawson, D., Lamond, N., Basner, M., Fomberstein, K., Dinges, D., Ogawa, K., Nittono, H., Yamazaki, K., Hori, T., Glamann, C., Hornung, O., Hansen, M.-L, Danker-Hopfe, H., Jung, C., Kecklund, G., Anund, A., Peters, B., Åkerstedt, T., Verster, J., Roehrs, T., Mets, M., de Senerpont Domis, L., Olivier, B., Volkerts, E., Knutson, K., Lauderdale, D., Rathouz, P., Christie, M., Chen, L., Bolortuya, Y., Lee, E., Mckenna, J., Mccarley, R., Strecker, R., Tamaki, M., Matsuoka, T., Aritake, S., Suzuki, H., Kuriyama, K., Ozaki, A., Abe, Y., Enomoto, M., Tagaya, H., Mishima, K., Matsuura, M., Uchiyama, M., Lima-Pacheco, E., Davis, K., Sabourin, C., Lortie-Lussier, M., de Koninck, J., van Der Werf, Y., van Der Helm, E., Schoonheim, M., van Someren, E., Tokley, M., Ball, M., Sato, T., Ghilardi, M. F., Moisello, C., Bove, M., Busi, M., Pelosin, E., Tononi, G., Eguchi, N., Sakata, M., Urade, Y., Doe, N., Yoshihara, K., Abe, K., Manabe, Y., Iwatsuki, K., Hayashi, T., Shoji, M., Kamiya, T., Gooley, J., Brainard, G., Rajaratnam, S., Kronauer, R., Czeisler, C., Lockley, S., Phillips, A., Robinson, P., Burgess, H., Revell, V., Eastman, C., Bihari, S., Ramakrishnan, N., Camerino, D., Conway, P. M., Costa, G., Vandewalle, G., Albouy, G., Sterpenich, V., Darsaud, A., Rauchs, G., Berken, P.-Y, Balteau, E., Maquet, P., Tendero, J. A., Domenech, M. P., Isern, F. S., Martínez, C., Roure, N., Sancho, E. E., Moreno, C. R., Silva, M., Marqueze, E. C., Waage, S., Bobko, N., Chernyuk, V., Yavorskiy, Y., Saxvig, I., Sørensen, E., de Mello, M. T., Esteves, A., Teixeira, C., Bittencourt, L. R., Silva, R., Pires, M. L., Mottram, V., Middelton, B., Arendt, J., Amaral, O., Rodrigues, M., Pereira, C., Tavares, I., Baba, K., Honma, S., Honma, K.-I., Yamanaka, Y., Hashimoto, S., Tanahashi, Y., Nishide, S.-Y, Honma, K.-I, Sletten, T., Middleton, B., Lederle, K., Skene, D., Roth, T., Walsh, J., Hogben, A., Ellis, J., Archer, S., von Schantz, M., Chen, N.-H., Wang, P.-C., Chen, C.-W., Lin, Y., Shih, T.-S., Armstrong, S., Redman, J., Stephan, E., David, M., Delanaud, S., Chardon, K., Libert, J.-P., Bach, V., Telliez, F., Reid, K., Jaksa, A., Eisengart, J., Kane, P., Naylor, E., Zee, P., Viola, A. U., de Valck, E., Hofmans, J., Theuns, P., Cluydts, R., Alexander, G., Karel, M., Christina, R., Sohn, I.-K., Cho, I. H., Kim, S. J., Yu, S.-H., Kim, H., Yoo, S. Y., Koh, S.-H., Cho, S.-J., Rotenberg, L., Silva-Costa, A., Griep, R. H., Amely, T., Kennedy, G. A., Pavlis, A., Thompson, B., Pierce, R., Howard, M., Briellmann, R., Venkateswaran, S., Blunden, S., Krawczyk, E., Blake, J., Gururajan, R., Kerr, D., Matuisi, T., Iwasaki, M., Yamasita, N., Iemura, A., Ohya, T., Yanagawa, T., Misa, R., Coleman, G., Conduit, R., Duce, B., Hukins, C., Nyandaiti, Y. W., Bamaki, S., Mohammed, A., Kwajarfa, S., Veeramachaneni, S. P., Murthy, A., Wilson, A., Maul, J., Hall, G., Stick, S., Moseley, L., Gradisar, M., Kurihara, T., Yamamoto, M., Yamamoto, S., Kuranari, M., Sparks, C. B., Bartle, A., Beckert, L., Latham-Smith, F. B., Hilton, J., Whitehead, B., Gulliver, T., Salvini, A., Grahame, S., Swift, M., Laybutt, N., Sharon, D., Mack, C., Hymell, B., Perrine, B., Ideshita, K., Taira, M., Matuo, A., Furutani, M., van Dongen, H., Mott, C., Huang, J.-K., Mollicone, D. J., Mckenzie, F., Dinges, David, Barnes, M., Rochford, P., Churchward, T., O’Donoghue, F., Penzel, T., Fietze, I., Canisius, S., Bekiaris, E., Terrill, P. I., Wilson, S., Suresh, S., Cooper, D., Suzuki, T., Ouchi, K., Moriya, A., Kameyama, K., Takahashi, M., Büttner, A., Rühle, K.-H., Wang, D., Wong, K., Dungan, II, G., Grunstein, R., Davidson, P., Jones, R., Gergely, V., Mashima, K., Miyazaki, S., Tanaka, T., Okawa, M., Yamada, N., Wyner, A., Raizen, D., Galante, R., Ng, A. K., Koh, T. S., Lim, L. L., Puvanendran, K., Peiris, M., Bones, P., Roebuck, T., Ho, S., Szollosi, I., Naughton, M., Williams, G., Parsley, C., Harris, M.-A., Thornton, A., Ruehland, W., Banks, S., Arroyo, S., Carroll, K., Pilmore, J., Stewart, C., Hamilton, G., van Acker, F., Cvetkovic, D., Holland, G., Cosic, I., Tolson, J., Worsnop, C., Cresswell, P., Hart, I., Bouarab, M., Delechelle, E., Drouot, X., Acebo, C., Singh, P., Lakey, T., Schachter, L., Rand, J., Collin, H., Snyder, E., Ma, J., Svetnick, V., Deacon, S., Dana, B., Konstanze, D., Uwe, M., Ingo, F., Thomas, P., Ivar, R., Mackiewicz, M., Shockley, K., Romer, M., Zimmerman, J., Baldwin, D., Jensen, S., Churchill, G., Paigen, B., Imeri, L., Ferrari, L., Bianchi, S., Dossena, S., Garofoli, A., Mangieri, M., Tagliavini, F., Forloni, G., Chiesa, R., Pedrazzoli, M., Pereira, D., Veauny, M., Bodenmann, S., Hohoff, C., Freitag, C., Deckert, J., Rétey, J., Landolt, H.-P., Strohl, K., Price, E., Yamauchi, M., Dostal, J., Feng, P., Han, F., Havekes, R., Novati, A., Hagewoud, R., Barf, P., van Der Borght, K., van Der Zee, E., Meerlo, P., Ruby, P., Caclin, A., Boulet, S., Delpuech, C., Morlet, D., Veasey, S., Aton, S., Jha, S., Coleman, T., Seibt, J., Frank, M., Lack, L., Churches, O., Feng, S. Y. S., Cassaglia, P., Yu, V. Y. H., Walker, A. M., Kohler, M., Kennedy, D., Martin, J., van Den Heuvel, C., Lushington, K., Herron, K., Khurana, C., Sterr, A., Olivadoti, M., Toth, L., Opp, M., Dang-Vu, T., Degueldre, C., Gais, S., Dang-Vu, T. T., Desseilles, M., Philips, C., Chijavadze, E., Babilodze, M., Chkhartishvili, E., Nachkebia, N., Mchedlidze, O., Dzadzamia, S., Griffiths, R., Walker, A., Horovitz, S., Fukunaga, M., Carr, W., Picchioni, D., de Zwart, J., van Gelderen, P., Braun, A., Duyn, J., Hanlon, E. H., Faraguna, U., Vyazovskiy, V., Cirelli, C., Ocampo-Garcés, A., Ibáñez, F., López, S., Vivaldi, E., Torrealba, F., Romanowski, C. P. N., Fenzl, T., Flachskamm, C., Deussing, J., Kimura, M., Tarokh, L., van Reen, E., Dorn, H., Velluti, R., Qu, W.-M., Huang, Z.-L., Hayaishi, O., Pedemonte, M., Drexler, D., Pol-Fernández, D., Bernhardt, V., Lopez, C., Rodriguez-Servetti, Z., Romanowski, C., Polta, S., Yassouridis, A., Abe, T., Takahashi, K., Koyama, Y., Kayama, Y., Lin, J.-S., Sakai, K., Gulia, K., Karashima, A., Shimazaki, M., Katayama, N., Nakao, M., Winsky-Sommerer, R., Knapman, A., Tobler, I., Altena, E., Sanz-Arigita, E., Chang, F.-C., Lu, C.-Y., Yi, P.-L., Hsiao, Y.-Z., Lowden, A., Nilsson, J., Hillert, L., Wiholm, C., Kuster, N., Arnetz, B., Szameitat, A., Shen, S., Daurat, A., Tiberge, M., Sok, N., D’Ortho, M. P. I. A., Karasinsky, P., Kohlmeier, K., Wess, J., Leonard, C., Kristensen, M., Kalinchuk, A., Porkka-Heiskanen, T., Mccarley, R. W., Basheer, R., Aizawa, R., Sunahara, H., Abe, S.-I., Iwaki, S., Houjyou, M., Satoh, M., Suda, H., Kheirandish-Gozal, L., Gozal, D., Walker, P., Noa, A., O’Driscoll, D., Ng, M., Yang, J., Davey, M., Anderson, V., Trinder, J., Horne, R., Sands, S., Kelly, V., Sia, K., Edwards, B., Skuza, E., Davidson, M., Berger, P. H. I. L. I. P., Wilkinson, M., Sánchez-Narváez, F., Gutiérrez, R., Camacho, L., Anaya, E., García-Campos, E., Labra, A., Domínguez, G., García-Polo, L., Haro, R., Verginis, N., Nixon, G., Baumert, M., Pamula, Y., Mihai, R., Wawurszak, M., Smith, N., Yiallourou, S., Andrew Ramsden, C., Williamson, B., Blecher, G., Teng, A., Dakin, C. Y. N., Yuil, M., Harris, M., Sadasivam, S., Bennison, J., Galland, B., Dawes, P., Taylor, B., Norman, M., Edwards, N., Harrison, H., Kol, C., Sullivan, C., Valladares, E., Macey, P., Kumar, R., Woo, M., Harper, R., Alger, J., Mcnamara, D., Tang, J., Goh, A., Teoh, O. H., Chiang, W. C., Chay, O. M., Marie Salvini, A., Riben, C., Blanck, A.-S., Marklund, M., Tourneux, P., Cardot, V., Leke, A., Iqbal, S. M., (Gus) Cooper, D., Witmans, M., Rodger, K., Thevasagayam, R., El-Hakim, H., Hill, C. M., Baya, A., Bucks, R., Kirkham, F., Virues-Ortega, J., Baldeweg, T., Paul, A., Hogan, A., Goodwin, J., Silva, G., Kaemingk, K., Sherrill, D., Morgan, W., Fregosi, R., Quan, S., Evans, C., Maclean, J., Waters, K., Fitzsimmons, D., Hayward, P., Fitzgerald, D., Terrill, G., O’Connell, A., Vannan, K., Richardson, H., Poluektov, M., Levin, I., Snegodskaya, M., Kolosova, N., Geppe, N., Nixon, G. Michelle, Thompson, J., Yhan, D., Becroft, D., Clark, P., Robinson, E., Waldie, K., Wild, C., Black, P., Stone, K., Britton, W., Chaves, Claudia, Tinoco, C., Goncalves, C., Ferreira, E., Santos, H., Boloto, J., Duarte, L., Paine, S., Wright, H., Slater, A., Rosen, G., Telliez, Frédéric, Djeddi, D., Kongolo, G., Degrugilliers, L., Horton, J., Buscemi, N., Vandermeer, B., Owens, J., Klassen, T., Gordon, J., King, N., Tripp, G., Oka, Y., Suzuki, S., de Lemos, M. C., Gonzaga, F. G., Shah, M. L., Bittencourt, L., Oliveira, L. V. Franco, Elshoff, J.-P., Braun, M., Andreas, J.-O., Strauss, B., Horstmann, R., Ahrweiler, S., Goldammer, N., Wada, M., Matsumoto, N., Rahman, M. D., Xu, X.-H., Makino, Y., Hashimoto, K., Zhang, M., Sastre, J.-P., Buda, C., Anaclet, C., Ohtsu, H., Danober, L., Desos, P., Cordi, A., Roger, A., Jacquet, A., Rogez, N., Thomas, J.-Y., Krentner, M., Boutin, J., Audinot-Bouchez, V., Baumann, C., Valko, P., Uhl, M., Hersberger, M., Rupp, T., Uchiyama, N., Nakamura, N., Konishi, T., Mcgrath, P., Fujiki, N., Tokunaga, J., Iijima, S., Nishino, S., Catherine, B.-R., Lely, F., Ralf, K., Oliver, N., François, J., Francois, J., Cedric, F., Changbin, Q., Patrick, H., Homanics, G., Heussler, H., Norris, R., Pache, D., Charles, B., Mcguire, T., Shelton, J., Bonaventure, P., Kelly, L., Aluisio, L., Lovenberg, T., Atack, J., Dugovic, C., Shapiro, C., Shen, J., Trajanovic, N., Chien, J., Verma, M., Fish, V., Wheatley, J., Amis, T., Alexiou, T., Wild, J., Bjursell, A., Solin, P., Sato, S., Matsubuchi, N., Gingras, M.-A., Labrosse, M., Chevrier, É, Lageix, P., Guay, M.-C., Braun, C., Godbout, R., Fatim, E. H., Loic, D., Stephane, D., Nathalie, L., Stéphane, D., Alain, G., Wiâm, R., Koabyashi, T., Tomita, S., Ishikawa, T., Manadai, O., Arakawa, K., Siato, Y., Bassi, A., Ocampo, A., Estrada, J., Blyton, D., O’Keeffe, K., Galletly, D., Larsen, P., Amatoury, J., Bilston, L., Kairaitis, K., Stephenson, R., Chu, K., Sekiguchi, Y., Suzuki, N., Yasuda, Y., Kodama, T., Honda, Y., Hsieh, K.-C., Lai, Y.-Y., Bannai, M., Kawai, N., Amici, R., Baracchi, F., Cerri, M., Del Sindaco, E., Dentico, D., Jones, C. A., Luppi, M., Martelli, D., Perez, E., Tazaki, M., Katayose, Y., Yasuda, K., Tokuyama, K., Maddison, K., Platt, P., Kirkness, J., Ware, J. C., May, J., Rosenthal, T., Park, G., Guibert, M., Allen, R. W., Cetin, T., Roman, V., Mollicone, D., Crummy, F., Cameron, P., Swann, P., Kossman, T., Taggart, F., Kandala, N.-B., Currie, A., Peile, E., Stranges, S., Marshall, N., Peltonen, M., Stenlof, K., Hedner, J., Sjostrom, L., Anderson, C., Platten, C., Jordan, K., Horne, J., Bjorkum, A., Kluge, B., Braseth, T., Gurvin, I., Kristensen, T., Nybo, R., Rosendahl, K., Nygaard, I., Biggs, S., Dollman, J., Kennedy, J. D., Martin, A. J., Haghighi, K. S., Bakht, N., Hyde, M., Harris, E., Zerouali, Y., Hosein, A., Jemel, B., Dodd, M., Rogers, N., Andersen, M., Martins, R., Alvarenga, T., Antunes, I., Papale, L., Killgore, W. S., Axelsson, J., Lekander, M., Ingre, M., Brismar, K., Dorrian, J., Ferguson, S., Jones, C., Buxton, O., Marcelli, E., Phipps-Nelson, J. O., Teixeira, L. R., de Castro Moreno, C., Turte, S. L., Nagai, R., do Rosário Dias De Oliveira Latorre, M., Marina, F., Paterson, J., Jackson, M., Johnston, P., Papafotiou, K., Croft, R., Dawson, S., Leenaars, C., Sandberg, H., Joosten, R., Dematteis, M., Feenstra, M., Wehrle, R., Rieger, M., Widmann, A., Dietl, T., Philipp, S., Wetter, T., Drummond, S., Czisch, M., Cairns, A., Lebourgeois, M., Harsh, J., Baulk, S., Vakulin, A., Catcheside, P., Antic, N., Mcevoy, D., Orff, H., Salamat, J., Meloy, M. J., Caron, A., Kostela, J., Purnell, M., Feyer, A.-M., Herbison, P., Saaresranta, T., Aittokallio, J., Karppinen, N., Toikka, J., Polo, O., Sallinen, M., Haavisto, M.-L., Hublin, C., Kiti, M., Jussi, V., Mikko, H., Chuah, L., Chee, M., Borges, F., Fischer, F., Moreno, C., Soares, N., Fonseca, M., Smolensky, M., Sackett-Lundeen, L., Haus, E., Nagata, N., Michael, N., Siccoli, M., Rogers, A., Hwang, W.-T., Scott, L., Dean, G., Geissler, E., Ametamey, S., Treyer, V., Wyss, M., Achermann, P., Schubiger, P., Theorell-Haglöw, J., Berne, C., Janson, C., Svensson, M., Lindberg, E., Caruso, H., Avinash, D., Minkel, J., Thompson, C., Wisor, J., Gerashchenko, D., Smith, K., Kuan, L., Pathak, S., Hawrylycz, M., Jones, A., Kilduff, T., Bergamo, C., Ecker, A., William, J., Niyogi, S., Coble, M., Goel, N., Lakhtman, L., Horswill, M., Whetton, M., Chambers, B., Signal, L., van Den Berg, M., Gander, P., Polotsky, V., Savransky, V., Bevans, S., Nanayakkara, A., Li, J.-G., Smith, P., Torbenson, M., Stockx, E., Brodecky, V., Berger, P., Chung-Mei Lam, J., Rial, R., Roca, C., Garau, C., Akaarir, M., Mccoy, J., Ward, C., Connolly, N., Tartar, J., Brown, R., Carberry, J., Bradford, A., O’Halloran, K., Mcguire, M., Nacher, M., Serrano-Mollar, A., Navajas, D., Farre, R., Montserrat, J., Fenik, V., Rukhadze, I., Kubin, L., Sivertsen, B., Overland, S., Mykletun, A., Czira, M., Fornádi, K., Lindner, A., Szeifert, L., Szentkirályi, A., Mucsi, I., Molnár, M., Novák, M., Zoller, R., Chin, K., Takegami, M., Oga, T., Nakayama-Asida, Y., Wakamura, T., Mishima, M., Fukuhara, S., Shepherd, K., Keir, G., Rixon, K., Makarie-Rofail, L., Unger, G., Svanborg, E., Harder, L., Sarberg, M., Broström, A., Josefsson, A., Herrera, A., Aguilera, L., Diaz, M., Fedson, A., Hung, J., Williams, C., Love, G., Middleton, S., Vermeulen, W., Middleton, P., Steinfort, D., Goldin, J., Eritaia, J., Dionysopoulos, P., Irving, L., Ciftci, T. U., Kokturk, O., Demirtas, S., Kanbay, A., Tavil, Y., Bukan, N., Demritas, S., Olsen, S., Douglas, J., Oei, T., Williams, S., Leung, S., Starmer, G., Lee, R., Chan, A., Dungan, G., Cistulli, P., Zeng, B., Bansal, A., Patial, K., Vijayan, V. K., Sonka, K., Fialova, L., Svarcova, J., Volna, J., Jiroutek, P., Pretl, M., Bartos, A., Hasegawa, R. A., Sasanabe, R., Nomura, A., Morita, M., Hori, R., Ohkura, Y., Shiomi, T. T., Collins, A., Jerums, G., Hare, D., Panagiotopoulos, S., Weatherhead, B., Bailey, M., Neil, C., Goldsworthy, U., Hill, C., Valencia-Flores, M., Resendiz, M., Juarez, S., Castano, A., Santiago, V., Aguilar, C., Ostrosky, F., Krum, H., Kaye, D., Neves, C., Decio, M., Monteiro, M., Cintra, F., Poyares, D., Viegas, C., Silva, C., Oliveira, H., Peixoto, T., Mikami, A., Watanabe, T., Kumano-Go, T., Adachi, H., Sugita, Y., Takeda, M., Oktay, B., Firat, H., Akbal, E., Ardic, S., Paim, S., Santos, R., Barrreto, A., Whitmore, H., Imperial, J., Temple, K., Rue, A., Hoffman, L., Liljenquist, D., Kazsa, K., Pavasovic, M., Copland, J., Ho, M., Jayamaha, J., Peverill, R., Hii, S., Hensley, M., Rowland, S., Windler, S., Johansson, M., Eriksson, P., Peker, Y., Råstam, L., Lindblad, U., Grote, L., Zou, D., Radlinski, J., Eder, D., Plens, C. M., Garcia Gonzaga, F. M., Farias Sa, P., Franco Oliveira, L. V., Faria Sa, P., Yoon, I.-Y., Chung, S., Hee Lee, C., Kim, J.-W., Faludi, B., Wang, X., Li, Q., Wan, H., Li, M., Pallayova, M., Donic, V., Tomori, Z., Ioacara, S., Olech, T., Mccallum, C., Bowes, M., Bowes, J., Chia, M., Gilbert, S. S., Sajkov, D., Teichtahl, H., Stevenson, I., Cunnington, D., Kalman, J., Szaboova, E., Higami, S., Kryger, M., Higami, Y., Suzuki, C., Kitano, H., Carin, S., Olof, S., Yngve, G., Gösta, B., Carlberg, B., Stenlund, H., Franklin, K. A., Oliveira, A., Vasconcelos, L., Martinez, D., Goncalves, S. C., Gus, M., Silva, E. O. A., Fuchs, S. C., Fuchs, F. D., Li, A., Au, J., Ho, C., Sung, R., Wing, Y., Tada, H., Terada, N., Togawa, K., Nakagawa, Y., Kishida, K., Kihara, S., Hirata, A., Sonoda, M., Nishizawa, H., Nakamura, T., Shimomura, I., Funahashi, T., Andrewartha, P., Sasse, A., Becker, M., Troester, N., Olschewski, H., Lisamayerkard, L., Glos, M., Blau, A., Peter, J.-G., Chesworth, W., Wilson, G., Piper, A., Chuang, L.-P., Lin, S.-W., Wang, C.-J., Li, H.-Y., Chou, Y.-T., Fu, J.-Y., Liao, Y.-F., Tsai, Y.-H., Chan, K., Laks, L., Nishibayashi, M., Miyamoto, M., Miyamoto, T., Hirata, K., Hoever, P., De Haas, S., Chiossi, E., Van Gerven, J., Dingemanse, J., Winkler, J., Cavallaro, M., Narui, K., Kasai, T., Dohl, T., Takaya, H., Kawana, F., Ueno, K., Panjwani, U., Thakur, L., Anand, J. P., Banerjee, P. K., Leigh, M., Paduch, A., Armstrong, J., Sampson, D., Kotajima, F., Mochizuki, T., Lorr, D., Harder, H., Chesworth, M., Becker, H., Abd-Elaty, N. M., Elprince, M., Ismail, N., Elserogi, W., Yeo, A., George, K., Thomson, K., Stadler, D., Bradley, J., Paul, D., Schwartz, A., Hagander, L., Harlid, R., Hultcrantz, E., Haraldsson, P., Cho, J.-G., Narayan, J., Nagarajah, M., Perri, R., Johnson, P., Burgess, K., Chau, N., Mcevoy, R. D., Arnardottir, E. S., Thorleifsdottir, B., Olafsson, I., Gislason, T., Tsuiki, S., Fujimatsu, S., Munezawa, T., Sato, Y., Subedi, P., Ainslie, P., Topor, Z., Whitelaw, W., Chan, M., So, H., Lam, H., Ng, S., Chan, I., Lam, C., Saigusa, H., Higurashi, N., He, Z. M., Cui, X. C., Li, J., Dong, X., Lv, Y., Zhou, M., Han, X., An, P., Wang, L., Macey, P. M., Serber, S., Cross, R., Yan-Go, F., Marshall, M., Rees, D., Lee, S. H., Ho Cho, J. I., Shin, C., Lee, J. Y., Kwon, S. Y., Kim, T.-H., Vedam, H., Barnes, D., Walter, H., Karin, J., Hermann, P., Belyavskiy, E., Galitsyn, P., Arbolishvili, G., Litvin, A., Chazova, I., Mareev, V., Ramar, K., Khan, A., Gay, P., Strömberg, A., Ulander, M., Fridlund, B., Mårtensson, J., Yee, B., Desai, A., Buchanan, P., Crompton, R., Melehan, K., Wong, P., Tee, A., Ng, A., Darendeliler, M. A., Ye, L., Maislin, G., Hurley, S., Mccluskey, S., Weaver, T., Yun, C.-H., Ji, K.-H., Ahn, J. Y., Lee, H.-W., Zhang, X., Yin, K., Zhaofang, G., Chong, L., Navailles, B., Zenou, E., Cheze, L., Pignat, J.-C., Tang, T., Remmers, J., Vasilakos, K., Denotti, A., Gilholme, J., Castronovo, V., Marelli, S., Aloia, M., Fantini, M. L., Kuo, T., Manconi, M., Zucconi, M., Ferini-Strambi, L., Livia Fantini, M., Giarolli, L., Oldani, A., Lee, Y., Trenell, M., Berend, N., Wang, M., Liang, Z., Lei, F., Komada, I., Nishikawa, M., Sriram, K., Mignone, L., Antic, R., Fujiwara, K., Beaudry, M., Gauthier, L., Laforte, M., Lavigne, G., Wylie, P., Orr, W., Grover, S., Geisler, P., Engelke, E., Cossa, G., Veitch, E., Brillante, R., Mcardle, N., Murphy, M., Singh, B., Gain, K., Maguire, C., Mutch, S., Brown, S., Asciuto, T., Newsam, C., Fransson, A., Ísacsson, G., Tsou, M.-C., Hsu, S.-P., Almendros, I., Acerbi, I., Vilaseca, I., Dcruz, O., Vaughn, B., Muenzer, J., Lacassagne, L., Montemayor, T., Roch-Paoli, J., Qian, J., Petocz, P., Chan, M. R., Munro, J., Zimmerman, M., Stanchina, M., Millman, R., Cassel, W., Ploch, T., Loh, A., Koehler, U., Jerrentrup, A., Greulich, T., Doyle, G., Pascoe, T., Jorgensen, G., Baglioni, C., Lombardo, C., Espie, C., Violani, C., Edell-Gustafsson, U., Swahn, E., Ejdeback, J., Tygesen, H., Johansson, A., Neckelmann, D., Hilde Nordhus, I., Zs-Kovács, Á., Vámos, E., Zs-Molnár, M., Maisuradze, L., Gugushvili, J., Darchia, N., Gvilia, I., Lortkipanidze, N., Oniani, N., Wang-Weigand, S., Mayer, G., Roth-Schechter, B., Hsu, S.-C., Yang, C.-M., Liu, C.-Y., Ito, H., Omvik, S., Nordhus, I. H., Farber, R., Scharf, M., Harris-Collazo, R., Pereira, J., Andras, S., Ohayon, M., David, B., Morgan, K., Voorn, T., Vis, J., Kuijer, J., Fortier-Brochu, E., Beaulieu-Bonneau, S., Ivers, H., Morin, C., Beaulieu-Benneau, S., Harris, J., Bartlett, D., Paisley, L., Moncada, S., Toelle, B., Bonnet, M. H., Arand, D., Bonnet, J., Bonnet, M., Doi, Y., Edéll-Gustafsson, U., Strijers, R., Fernando, A., Arroll, B., Warman, G., Funakura, M., Shikano, S., Unemoto, Y., Fujisawa, M., Hong, S.-C., Jeong, J.-H., Shin, Y.-K., Han, J.-H., Lee, S.-P., Lee, J.-H., Mignot, E., Nakajima, T., Hayashida, K., Honda, M., Ardestani, P., Etemadifar, M., Nejadnik, H., Maghzi, A. H., Basiri, K., Ebrahimi, A., Davoodi, M., Peraita-Adrados, R., Vicario, J. L., Shin, H.-B., Marti, I., Carriero, L., Fulda, S., Beitinger, P., Pollmacher, T., Lam, J. S. P., Fong, S. Y. Y., Tang, N. L. S., Ho, C. K. W., Li, A. M. C., Wing, Y. K., Guilleminault, C., Black, J., Wells, C., Kantor, S., Janisiewicz, A., Scammell, T., Tanaka, S., Smith, A., Neufing, P., Gordon, T., Fuller, P., Gompf, H., Pedersen, N., Saper, C., Lu, J., Sasai, T., Donjacour, C., Fronczek, R., Le Cessie, S., Lammers, G. J., van Dijk, J. G., Hayashi-Ogawa, Y., Okuda, M., Lam, V. K.-H., Chen, A. L., Ho, C. K.-W., Wing, Y.-K., Lehrhaft, B., Brilliante, R., van Der Zande, W., Overeem, S., van Dijk, G., Lammers, J. G., Opazo, C. J., Jeong, D.-U., Sung, Y. H., Lyoo, I. K., Takahashi, Y., Murasaki, M., Bloch, K., Jung, H., Dahab, M. M., Campos, T. F., Mccabe, S., Maravic, K., Wiggs, L., Connelly, V., Barnes, J., Saito, Y., Ogawa, M., Murata, M., Nadig, U., Rahman, A., Aritake, K., D’Cruz, O., Suzuki, K., Kaji, Y., Takekawa, H., Nomura, T., Yasui, K., Nakashima, K., Bahammam, A., Rab, M. G., Owais, S., Alsuwat, K., Hamam, K., Zs, M., Boroojerdi, B., Giladi, N., Wood, D., Sherman, D., Chaudhuri, R., Partinen, M., Abdo, F., Bloem, B., Kremer, B., Verbeek, M., Cronlein, T., Mueller, U., Hajak, G., Zulley, J., Namba, K., Li, L., Mtsuura, M., Kaneita, Y., Ohida, T., Cappeliez, B., Moutrier, R., De, S., Dwivedi, S., Chambers, D., Gabbay, E., Watanabe, A., Valle, C., Kauati, A., Watanabe, R., Chediek, F., Botte, S., Azevedo, E., Kempf, J., Cizza, G., Torvik, S., Brancati, G., Smirne, N., Bruni, A., Goff, E., Freilich, S., Malaweera, A., Simonds, A., Mathias, C., Morrell, M., Rinsky, B., Fonarow, G., Gradinger, F. P., Boldt, C., Geyh, S., Stucki, A., Dahlberg, A., Michel, F., Savard, M.-H., Savard, J., Quesnel, C., Hirose, K., Takahara, M., Mizuno, K., Sadachi, H., Nagashima, Y., Yada, Y., Cheung, C.-F., Lau, C., Lai, W., Sin, K., Tam, C., Hellgren, J., Omenaas, E., Gíslason, T., Jögi, R., Franklin, K., Torén, K., Wang, F., Kadono, M., Shigeta, M., Nakazawa, A., Ueda, M., Fukui, M., Hasegawa, G., Yoshikawa, T., de Niet, G., Tiemens, B., Lendemeijer, B., Hutschemaekers, G., Gauthier, A.-K., Chevrette, T., Chevrier, E., Bouvier, H., Parry, B., Meliska, C., Nowakowski, S., Lopez, A., Martinez, F., Sorenson, D., Lien, M. L., Lattova, Z., Maurovich-Horvat, E., Nia, S., Pollmächer, T., Poulin, J., Chouinard, S., Stip, E., Guillem, F., Venne, D., Caouette, M., Lamont, M.-E., Lázár, A., Lázár, Z., Bíró, A., Gyõri, M., Tárnok, Z., Prekop, C., Gádoros, J., Halász, P., Bódizs, R., Okun, M., Hanusa, B., Hall, M., Wisner, K., Pereira, M., Kumar, R. A. J. E. S. H., Macey, P. A. U. L., Woo, M. A. R. Y., Serber, S. T. A. C. Y., Valladares, E. D. W. I. N., Harper, R. E. B. E. C. C. A., Harper, R. O. N. A. L. D., Puttonen, S., Härmä, M., Vahtera, J., Kivimäki, M., Lamarche, L., Hemmeter, U. M., Thum, A., Rocamora, R., Giesler, M., Haag, A., Dodel, R., Krieg, J. C., Shechter, A., L’Esperance, P., Boivin, D. B., Vu, M.-T., and Richards, H.

Published
2007
Full Text
View/download PDF

5. Conserved UBE3A subcellular distribution between human and mice is facilitated by non-homologous isoforms

Author

Zampeta, F. Isabella, Sonzogni, Monica, Niggl, Eva, Lendemeijer, B. (Bas), Smeenk, H.G., Vrij, F.M.S. (Femke), Kushner, S.A. (Steven), Distel, Ben, Elgersma, Y. (Ype), Zampeta, F. Isabella, Sonzogni, Monica, Niggl, Eva, Lendemeijer, B. (Bas), Smeenk, H.G., Vrij, F.M.S. (Femke), Kushner, S.A. (Steven), Distel, Ben, and Elgersma, Y. (Ype)

Abstract

The human UBE3A gene, which is essential for normal neurodevelopment, encodes three Ubiquitin E3 ligase A (UBE3A) protein isoforms. However, the subcellular localization and relative abundance of these human UBE3A isoforms are unknown. We found, as previously reported in mice, that UBE3A is predominantly nuclear in human neurons. However, this conserved subcellular distribution is achieved by strikingly distinct cis-acting mechanisms. A single amino-acid deletion in the N-terminus of human hUBE3A-Iso3, which is homologous to cytosolic mouse mUBE3A-Iso2, results in its translocation to the nucleus. This singe amino-acid deletion is shared with apes and Old World monkeys and was preceded by the appearance of the cytosolic hUBE3A-Iso2 isoform. This hUBE3A-Iso2 isoform arose after the lineage of New World monkeys and Old World monkeys separated from the Tarsiers (Tarsiidae). Due to the loss of a si

Published
2020
Full Text
View/download PDF

8. Novel genetic loci affecting facial shape variation in humans

Author

Xiong, Z. (Ziyi), Dankova, G. (Gabriela), Howe, L.J. (Laurence J.), Lee, M.K. (Myoung Keun), Hysi, P.G. (Pirro G.), Jong, M.A. (Markus) de, Zhu, G. (Gu), Adhikari, K. (Kaustubh), Li, D. (Dan), Li, Y. (Yi), Pan, B. (Bo), Feingold, E. (Eleanor), Marazita, M.L. (Mary), Shaffer, J.R. (John R), McAloney, K. (Kerrie), Xu, S. (Shuhua), Jin, L. (Li), Wang, S. (Sijia), Vrij, F.M.S. (Femke), Lendemeijer, B. (Bas), Richmond, S. (Stephen), Zhurov, A. (Alexei), Lewis, S. (Sarah), Sharp, G.C. (Gemma C.), Paternoster, L. (Lavinia), Thompson, H. (Holly), Gonzalez-Jose, R. (Rolando), Bortolini, M.C. (Maria Catira), Canizales-Quinteros, S. (Samuel), Gallo, C. (Carla), Poletti, G. (Giovanni), Bedoya, E.G. (Elsie), Rothhammer, F. (Francisco), Uitterlinden, A.G. (André), Ikram, M.A. (Arfan), Wolvius, E.B. (Eppo), Kushner, S.A. (Steven), Nijsten, T.E.C. (Tamar), Palstra, R.-J.T.S. (Robert-Jan), Boehringer, S. (Stefan), Medland, S.E. (Sarah), Tang, K. (Kun), Ruiz-Linares, A. (Andres), Martin, N.G. (Nicholas), Spector, T.D. (Timothy), Stergiakouli, E. (Evie), Weinberg, S.M. (Seth M.), Liu, F. (Fan), Kayser, M.H. (Manfred), Xiong, Z. (Ziyi), Dankova, G. (Gabriela), Howe, L.J. (Laurence J.), Lee, M.K. (Myoung Keun), Hysi, P.G. (Pirro G.), Jong, M.A. (Markus) de, Zhu, G. (Gu), Adhikari, K. (Kaustubh), Li, D. (Dan), Li, Y. (Yi), Pan, B. (Bo), Feingold, E. (Eleanor), Marazita, M.L. (Mary), Shaffer, J.R. (John R), McAloney, K. (Kerrie), Xu, S. (Shuhua), Jin, L. (Li), Wang, S. (Sijia), Vrij, F.M.S. (Femke), Lendemeijer, B. (Bas), Richmond, S. (Stephen), Zhurov, A. (Alexei), Lewis, S. (Sarah), Sharp, G.C. (Gemma C.), Paternoster, L. (Lavinia), Thompson, H. (Holly), Gonzalez-Jose, R. (Rolando), Bortolini, M.C. (Maria Catira), Canizales-Quinteros, S. (Samuel), Gallo, C. (Carla), Poletti, G. (Giovanni), Bedoya, E.G. (Elsie), Rothhammer, F. (Francisco), Uitterlinden, A.G. (André), Ikram, M.A. (Arfan), Wolvius, E.B. (Eppo), Kushner, S.A. (Steven), Nijsten, T.E.C. (Tamar), Palstra, R.-J.T.S. (Robert-Jan), Boehringer, S. (Stefan), Medland, S.E. (Sarah), Tang, K. (Kun), Ruiz-Linares, A. (Andres), Martin, N.G. (Nicholas), Spector, T.D. (Timothy), Stergiakouli, E. (Evie), Weinberg, S.M. (Seth M.), Liu, F. (Fan), and Kayser, M.H. (Manfred)

Abstract

The human face represents a combined set of highly heritable phenotypes, but knowledge on its genetic architecture remains limited, despite the relevance for various fields. A series of genome-wide association studies on 78 facial shape phenotypes quantified from 3-dimensional facial images of 10,115 Europeans identified 24 genetic loci reaching study-wide suggestive association (p < 5 × 10-8), among which 17 were previously unreported. A follow-up multi-ethnic study in additional 7917 individuals confirmed 10 loci including six unreported ones (padjusted < 2.1 × 10-3). A global map of derived polygenic face scores assembled facial features in major continental groups consistent with anthropological knowledge. Analyses of epigenomic datasets from cranial neural crest cells revealed abundant cis-regulatory activities at the face-associated genetic loci. Luciferase reporter assays in neural crest progenitor cells highlighted enhancer activities of several face-associated DNA variants. These results substantially advance our understanding of the genetic basis underlying human facial variation and provide candidates for future in-vivo functional studies.

Published
2019
Full Text
View/download PDF

9. Candidate CSPG4 mutations and induced pluripotent stem cell modeling implicate oligodendrocyte progenitor cell dysfunction in familial schizophrenia

Author

Vrij, F.M.S. (Femke), Bouwkamp, C.G. (Christian), Gunhanlar, N. (Nilhan), Shpak, G. (Guy), Lendemeijer, B. (Bas), Baghdadi, M. (Maarouf), Gopalakrishna, S. (Shreekara), Ghazvini, M. (Mehrnaz), Li, T. (Tracy), Quadri, M. (Marialuisa), Olgiati, S. (Simone), Breedveld, G.J. (Guido), Coesmans, M.P.H. (Michiel), Mientjes, E.J. (Edwin), de Wit, T. (Ton), Verheijen, F.W. (Frans), Beverloo, H.B. (Berna), Cohen, D. (Dan), Kok, R.M. (Rob M.), Bakker, P.R. (Roberto), Nijburg, A. (Aviva), Spijker, A.T. (Anne), Haffmans, P.M.J. (P.M. Judith), Hoencamp, E. (Erik), Bergink, V. (Veerle), Vorstman, J.A.S., Wu, T. (Timothy), Olde Loohuis, L.M. (Loes M.), Amin, N. (Najaf), Langen, C.D. (Carolyn), Hofman, A. (Albert), Hoogendijk, W.J.G. (Witte), van Duijn, C.M. (Cornelia M.), Ikram, M.A. (M. A.), Vernooij, M.W. (Meike), Tiemeier, H.W. (Henning), Uitterlinden, A.G. (André G.), Elgersma, Y. (Ype), Distel, B. (Ben), Gribnau, J.H. (Joost), White, T.J.H. (Tonya), Bonifati, V. (Vincenzo), Kushner, S.A. (Steven A.), Vrij, F.M.S. (Femke), Bouwkamp, C.G. (Christian), Gunhanlar, N. (Nilhan), Shpak, G. (Guy), Lendemeijer, B. (Bas), Baghdadi, M. (Maarouf), Gopalakrishna, S. (Shreekara), Ghazvini, M. (Mehrnaz), Li, T. (Tracy), Quadri, M. (Marialuisa), Olgiati, S. (Simone), Breedveld, G.J. (Guido), Coesmans, M.P.H. (Michiel), Mientjes, E.J. (Edwin), de Wit, T. (Ton), Verheijen, F.W. (Frans), Beverloo, H.B. (Berna), Cohen, D. (Dan), Kok, R.M. (Rob M.), Bakker, P.R. (Roberto), Nijburg, A. (Aviva), Spijker, A.T. (Anne), Haffmans, P.M.J. (P.M. Judith), Hoencamp, E. (Erik), Bergink, V. (Veerle), Vorstman, J.A.S., Wu, T. (Timothy), Olde Loohuis, L.M. (Loes M.), Amin, N. (Najaf), Langen, C.D. (Carolyn), Hofman, A. (Albert), Hoogendijk, W.J.G. (Witte), van Duijn, C.M. (Cornelia M.), Ikram, M.A. (M. A.), Vernooij, M.W. (Meike), Tiemeier, H.W. (Henning), Uitterlinden, A.G. (André G.), Elgersma, Y. (Ype), Distel, B. (Ben), Gribnau, J.H. (Joost), White, T.J.H. (Tonya), Bonifati, V. (Vincenzo), and Kushner, S.A. (Steven A.)

Abstract

Schizophrenia is highly heritable, yet its underlying pathophysiology remains largely unknown. Among the most well-replicated findings in neurobiological studies of schizophrenia are deficits in myelination and white matter integrity; however, direct etiological genetic and cellular evidence has thus far been lacking. Here, we implement a family-based approach for genetic discovery in schizophrenia combined with functional analysis using induced pluripotent stem cells (iPSCs). We observed familial segregation of two rare missense mutations in Chondroitin Sulfate Proteoglycan 4 (CSPG4) (c.391G > A [p.A131T], MAF 7.79 × 10−5 and c.2702T > G [p.V901G], MAF 2.51 × 10−3). The CSPG4A131T mutation was absent from the Swedish Schizophrenia Exome Sequencing Study (2536 cases, 2543 controls), while the CSPG4V901G mutation was nominally enriched in cases (11 cases vs. 3 controls, P = 0.026, OR 3.77, 95% CI 1.05–13.52). CSPG4/NG2 is a hallmark protein of oligodendrocyte progenitor cells (OPCs). iPSC-derived OPCs from CSPG4A131T mutation carriers exhibited abnormal post-translational processing (P = 0.029), subcellular localization of mutant NG2 (P = 0.007), as well as aberrant cellular morphology (P = 3.0 × 10−8), viability (P = 8.9 × 10−7), and myelination potential (P = 0.038). Moreover, transfection of healthy non-carrier sibling OPCs confirmed a pathogenic effect on cell survival of both the CSPG4A131T (P = 0.006) and CSPG4V901G (P = 3.4 × 10−4) mutations. Finally, in vivo diffusion tensor imaging of CSPG4A131T mutation carriers demonstrated a reduction of brain white matter integrity compared to unaffected sibling and matched general population controls (P = 2.2 × 10−5). Together, our findings provide a convergence of genetic and functional evidence to implicate OPC dysfunction as a candidate pathophysiological mechanism of familial schizophrenia.

Published
2018
Full Text
View/download PDF

10. SOX10 Single Transcription Factor-Based Fast and Efficient Generation of Oligodendrocytes from Human Pluripotent Stem Cells

Author

García-León, J.A. (Juan Antonio), Kumar, M. (Manoj), Boon, R. (Ruben), Chau, D. (David), One, J. (Jennifer), Wolfs, E. (Esther), Eggermont, K. (Kristel), Berckmans, P. (Pieter), Gunhanlar, N. (Nilhan), Vrij, F.M.S. (Femke), Lendemeijer, B. (Bas), Pavie, B. (Benjamin), Corthout, N. (Nikky), Kushner, S.A. (Steven A.), Dávila, J.C. (José Carlos), Lambrichts, I. (Ivo), Hu, W.-S. (Wei-Shou), Verfaillie, C.M. (Catherine M.), García-León, J.A. (Juan Antonio), Kumar, M. (Manoj), Boon, R. (Ruben), Chau, D. (David), One, J. (Jennifer), Wolfs, E. (Esther), Eggermont, K. (Kristel), Berckmans, P. (Pieter), Gunhanlar, N. (Nilhan), Vrij, F.M.S. (Femke), Lendemeijer, B. (Bas), Pavie, B. (Benjamin), Corthout, N. (Nikky), Kushner, S.A. (Steven A.), Dávila, J.C. (José Carlos), Lambrichts, I. (Ivo), Hu, W.-S. (Wei-Shou), and Verfaillie, C.M. (Catherine M.)

Abstract

Scarce access to primary samples and lack of efficient protocols to generate oligodendrocytes (OLs) from human pluripotent stem cells (hPSCs) are hampering our understanding of OL biology and the development of novel therapies. Here, we demonstrate that overexpression of the transcription factor SOX10 is sufficient to generate surface antigen O4-positive (O4+) and myelin basic protein-positive OLs from hPSCs in only 22 days, including from patients with multiple sclerosis or amyotrophic lateral sclerosis. The SOX10-induced O4+ population resembles primary human OLs at the transcriptome level and can myelinate neurons in vivo. Using in vitro OL-neuron co-cultures, myelination of neurons by OLs can also be demonstrated, which can be adapted to a high-throughput screening format to test the response of pro-myelinating drugs. In conclusion, we provide an approach to generate OLs in a very rapid and efficient manner, which can be used for disease modeling, drug discovery efforts, and potentially for therapeutic OL transplantation. In this article, García-León JA and colleagues demonstrate the generation of functional oligodendrocytes (OLs) from human pluripotent stem cells in a rapid and efficient manner by the single overexpression of SOX10. Generated OLs resemble primary OLs at the transcriptome level and can myelinate neurons both in vivo and in vitro. Neuron-OL co-cultures, adapted to high-throughput screening formats, responded to drugs affecting myelination.

Published
2018
Full Text
View/download PDF

12. A simplified protocol for differentiation of electrophysiologically mature neuronal networks from human induced pluripotent stem cells

Author

Gunhanlar, N, primary, Shpak, G, additional, van der Kroeg, M, additional, Gouty-Colomer, L A, additional, Munshi, S T, additional, Lendemeijer, B, additional, Ghazvini, M, additional, Dupont, C, additional, Hoogendijk, W J G, additional, Gribnau, J, additional, de Vrij, F M S, additional, and Kushner, S A, additional

Published
2017
Full Text
View/download PDF

15. A simplified protocol for differentiation of electrophysiologically mature neuronal networks from human induced pluripotent stem cells

Author

Gunhanlar, N, Shpak, G, van der Kroeg, M, Gouty-Colomer, L A, Munshi, S T, Lendemeijer, B, Ghazvini, M, Dupont, C, Hoogendijk, W J G, Gribnau, J, de Vrij, F M S, and Kushner, S A

Abstract

Progress in elucidating the molecular and cellular pathophysiology of neuropsychiatric disorders has been hindered by the limited availability of living human brain tissue. The emergence of induced pluripotent stem cells (iPSCs) has offered a unique alternative strategy using patient-derived functional neuronal networks. However, methods for reliably generating iPSC-derived neurons with mature electrophysiological characteristics have been difficult to develop. Here, we report a simplified differentiation protocol that yields electrophysiologically mature iPSC-derived cortical lineage neuronal networks without the need for astrocyte co-culture or specialized media. This protocol generates a consistent 60:40 ratio of neurons and astrocytes that arise from a common forebrain neural progenitor. Whole-cell patch-clamp recordings of 114 neurons derived from three independent iPSC lines confirmed their electrophysiological maturity, including resting membrane potential (−58.2±1.0 mV), capacitance (49.1±2.9 pF), action potential (AP) threshold (−50.9±0.5 mV) and AP amplitude (66.5±1.3 mV). Nearly 100% of neurons were capable of firing APs, of which 79% had sustained trains of mature APs with minimal accommodation (peak AP frequency: 11.9±0.5 Hz) and 74% exhibited spontaneous synaptic activity (amplitude, 16.03±0.82 pA; frequency, 1.09±0.17 Hz). We expect this protocol to be of broad applicability for implementing iPSC-based neuronal network models of neuropsychiatric disorders.

Published
2018
Full Text
View/download PDF

17. Eerst medicatie, dan pas naar buiten: afspraak is afspraak?

Author

Abma, T., Widdershoven, G., Lendemeijer, B., Gremmen, C.C.M., Nederpelt, G. van, Bauduin, D., Abma, T., Widdershoven, G., Lendemeijer, B., Gremmen, C.C.M., Nederpelt, G. van, and Bauduin, D.

Abstract

Item does not contain fulltext

Published
2004

18. Music-assisted relaxation to improve sleep quality: meta-analysis.

Author

de Niet G, Tiemens B, Lendemeijer B, and Hutschemaekers G

Subjects
SOMNOLOGY, NURSING research, MUSIC for relaxation, MUSIC therapy, META-analysis
Abstract

Title. Music-assisted relaxation to improve sleep quality: meta-analysis. Aim. This paper is a report of a meta-analysis conducted to evaluate the efficacy of music-assisted relaxation for sleep quality in adults and elders with sleep complaints with or without a co-morbid medical condition. Background. Clinical studies have shown that music can influence treatment outcome in a positive and beneficial way. Music holds the promise of counteracting psychological presleep arousal and thus improving the preconditions for sleep. Data sources. We conducted a search in the Embase (1997 - July 2008), Medline (1950 - July 2008), Cochrane (2000 - July 2008), Psychinfo (1987 - July 2008) and Cinahl (1982 - July 2008) databases for randomized controlled trials reported in English, German, French and Dutch. The outcome measure of interest was sleep quality. Methods. Data were extracted from the included studies using predefined data fields. The researchers independently assessed the quality of the trials using the Delphi list. Only studies with a score of 5 points or higher were included. A pooled analysis was performed based on a fixed effect model. Results. Five randomized controlled trials with six treatment conditions and a total of 170 participants in intervention groups and 138 controls met our inclusion criteria. Music-assisted relaxation had a moderate effect on the sleep quality of patients with sleep complaints (standardized mean difference, -0·74; 95% CI: -0·96, -0·46). Subgroup analysis revealed no statistically significant contribution of accompanying measures. Conclusion. Music-assisted relaxation can be used without intensive investment in training and materials and is therefore cheap, easily available and can be used by nurses to promote music-assisted relaxation to improve sleep quality. [ABSTRACT FROM AUTHOR]

Published
2009
Full Text
View/download PDF

19. Human Pluripotent Stem Cell-Derived Astrocyte Functionality Compares Favorably with Primary Rat Astrocytes.

Author

Lendemeijer B, Unkel M, Smeenk H, Mossink B, Hijazi S, Gordillo-Sampedro S, Shpak G, Slump DE, van den Hout MCGN, van IJcken WFJ, Bindels EMJ, Hoogendijk WJG, Nadif Kasri N, de Vrij FMS, and Kushner SA

Subjects
Humans, Animals, Rats, Cells, Cultured, Neural Stem Cells physiology, Cell Differentiation physiology, Astrocytes physiology, Coculture Techniques, Pluripotent Stem Cells physiology, Neurons physiology
Abstract

Astrocytes are essential for the formation and maintenance of neural networks. However, a major technical challenge for investigating astrocyte function and disease-related pathophysiology has been the limited ability to obtain functional human astrocytes. Despite recent advances in human pluripotent stem cell (hPSC) techniques, primary rodent astrocytes remain the gold standard in coculture with human neurons. We demonstrate that a combination of leukemia inhibitory factor (LIF) and bone morphogenetic protein-4 (BMP4) directs hPSC-derived neural precursor cells to a highly pure population of astroglia in 28 d. Using single-cell RNA sequencing, we confirm the astroglial identity of these cells and highlight profound transcriptional adaptations in cocultured hPSC-derived astrocytes and neurons, consistent with their further maturation. In coculture with human neurons, multielectrode array recordings revealed robust network activity of human neurons in a coculture with hPSC-derived or rat astrocytes [3.63 ± 0.44 min -1 (hPSC-derived), 2.86 ± 0.64 min -1 (rat); p  = 0.19]. In comparison, we found increased spike frequency within network bursts of human neurons cocultured with hPSC-derived astrocytes [56.31 ± 8.56 Hz (hPSC-derived), 24.77 ± 4.04 Hz (rat); p  < 0.01], and whole-cell patch-clamp recordings revealed an increase of postsynaptic currents [2.76 ± 0.39 Hz (hPSC-derived), 1.07 ± 0.14 Hz (rat); p  < 0.001], consistent with a corresponding increase in synapse density [14.90 ± 1.27/100 μm 2 (hPSC-derived), 8.39 ± 0.63/100 μm 2 (rat); p  < 0.001]. Taken together, we show that hPSC-derived astrocytes compare favorably with rat astrocytes in supporting human neural network activity and maturation, providing a fully human platform for investigating astrocyte function and neuronal-glial interactions., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Lendemeijer et al.)

Published
2024
Full Text
View/download PDF

20. Standardizing designed and emergent quantitative features in microphysiological systems.

Author

Nahon DM, Moerkens R, Aydogmus H, Lendemeijer B, Martínez-Silgado A, Stein JM, Dostanić M, Frimat JP, Gontan C, de Graaf MNS, Hu M, Kasi DG, Koch LS, Le KTT, Lim S, Middelkamp HHT, Mooiweer J, Motreuil-Ragot P, Niggl E, Pleguezuelos-Manzano C, Puschhof J, Revyn N, Rivera-Arbelaez JM, Slager J, Windt LM, Zakharova M, van Meer BJ, Orlova VV, de Vrij FMS, Withoff S, Mastrangeli M, van der Meer AD, and Mummery CL

Subjects
Humans, Animals, Microfluidic Analytical Techniques instrumentation, Microfluidic Analytical Techniques methods, Microfluidics methods, Models, Biological, Brain physiology, Equipment Design, Microphysiological Systems, Lab-On-A-Chip Devices
Abstract

Microphysiological systems (MPSs) are cellular models that replicate aspects of organ and tissue functions in vitro. In contrast with conventional cell cultures, MPSs often provide physiological mechanical cues to cells, include fluid flow and can be interlinked (hence, they are often referred to as microfluidic tissue chips or organs-on-chips). Here, by means of examples of MPSs of the vascular system, intestine, brain and heart, we advocate for the development of standards that allow for comparisons of quantitative physiological features in MPSs and humans. Such standards should ensure that the in vivo relevance and predictive value of MPSs can be properly assessed as fit-for-purpose in specific applications, such as the assessment of drug toxicity, the identification of therapeutics or the understanding of human physiology or disease. Specifically, we distinguish designed features, which can be controlled via the design of the MPS, from emergent features, which describe cellular function, and propose methods for improving MPSs with readouts and sensors for the quantitative monitoring of complex physiology towards enabling wider end-user adoption and regulatory acceptance., (© 2024. Springer Nature Limited.)

Published
2024
Full Text
View/download PDF

21. iPSC-derived healthy human astrocytes selectively load miRNAs targeting neuronal genes into extracellular vesicles.

Author

Gordillo-Sampedro S, Antounians L, Wei W, Mufteev M, Lendemeijer B, Kushner SA, de Vrij FMS, Zani A, and Ellis J

Subjects
Humans, Cell Differentiation, Cells, Cultured, Neural Stem Cells metabolism, Neural Stem Cells cytology, Extracellular Vesicles metabolism, Induced Pluripotent Stem Cells metabolism, MicroRNAs metabolism, MicroRNAs genetics, Astrocytes metabolism, Neurons metabolism
Abstract

Astrocytes are in constant communication with neurons during the establishment and maturation of functional networks in the developing brain. Astrocytes release extracellular vesicles (EVs) containing microRNA (miRNA) cargo that regulates transcript stability in recipient cells. Astrocyte released factors are thought to be involved in neurodevelopmental disorders. Healthy astrocytes partially rescue Rett Syndrome (RTT) neuron function. EVs isolated from stem cell progeny also correct aspects of RTT. EVs cross the blood-brain barrier (BBB) and their cargo is found in peripheral blood which may allow non-invasive detection of EV cargo as biomarkers produced by healthy astrocytes. Here we characterize miRNA cargo and sequence motifs in healthy human astrocyte derived EVs (ADEVs). First, human induced Pluripotent Stem Cells (iPSC) were differentiated into Neural Progenitor Cells (NPCs) and subsequently into astrocytes using a rapid differentiation protocol. iPSC derived astrocytes expressed specific markers, displayed intracellular calcium transients and secreted ADEVs. miRNAs were identified by RNA-Seq on astrocytes and ADEVs and target gene pathway analysis detected brain and immune related terms. The miRNA profile was consistent with astrocyte identity, and included approximately 80 miRNAs found in astrocytes that were relatively depleted in ADEVs suggestive of passive loading. About 120 miRNAs were relatively enriched in ADEVs and motif analysis discovered binding sites for RNA binding proteins FUS, SRSF7 and CELF5. miR-483-5p was the most significantly enriched in ADEVs. This miRNA regulates MECP2 expression in neurons and has been found differentially expressed in blood samples from RTT patients. Our results identify potential miRNA biomarkers selectively sorted into ADEVs and implicate RNA binding protein sequence dependent mechanisms for miRNA cargo loading., Competing Interests: Declaration of competing interest The authors declare they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2024
Full Text
View/download PDF

22. In vitro and in vivo differences in neurovirulence between D614G, Delta And Omicron BA.1 SARS-CoV-2 variants.

Author

Bauer L, Rissmann M, Benavides FFW, Leijten L, van Run P, Begeman L, Veldhuis Kroeze EJB, Lendemeijer B, Smeenk H, de Vrij FMS, Kushner SA, Koopmans MPG, Rockx B, and van Riel D

Subjects
Animals, Cricetinae, Humans, Mesocricetus, SARS-CoV-2, COVID-19, Induced Pluripotent Stem Cells
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with various neurological complications. Although the mechanism is not fully understood, several studies have shown that neuroinflammation occurs in the acute and post-acute phase. As these studies have predominantly been performed with isolates from 2020, it is unknown if there are differences among SARS-CoV-2 variants in their ability to cause neuroinflammation. Here, we compared the neuroinvasiveness, neurotropism and neurovirulence of the SARS-CoV-2 ancestral strain D614G, the Delta (B.1.617.2) and Omicron BA.1 (B.1.1.529) variants using in vitro and in vivo models. The Omicron BA.1 variant showed reduced neurotropism and neurovirulence compared to Delta and D614G in human induced pluripotent stem cell (hiPSC)-derived cortical neurons co-cultured with astrocytes. Similar differences were obtained in Syrian hamsters inoculated with D614G, Delta and the Omicron BA.1 variant 5 days post infection. Replication in the olfactory mucosa was observed in all hamsters, but most prominently in D614G inoculated hamsters. Furthermore, neuroinvasion into the CNS via the olfactory nerve was observed in D614G, but not Delta or Omicron BA.1 inoculated hamsters. Furthermore, neuroinvasion was associated with neuroinflammation in the olfactory bulb of hamsters inoculated with D614G. Altogether, our findings suggest differences in the neuroinvasive, neurotropic and neurovirulent potential between SARS-CoV-2 variants using in vitro hiPSC-derived neural cultures and in vivo in hamsters during the acute phase of the infection., (© 2022. The Author(s).)

Published
2022
Full Text
View/download PDF

23. Replication Kinetics, Cell Tropism, and Associated Immune Responses in SARS-CoV-2- and H5N1 Virus-Infected Human Induced Pluripotent Stem Cell-Derived Neural Models.

Author

Bauer L, Lendemeijer B, Leijten L, Embregts CWE, Rockx B, Kushner SA, de Vrij FMS, and van Riel D

Subjects
Animals, Brain Diseases etiology, COVID-19 complications, Chlorocebus aethiops, Dogs, Humans, Influenza A Virus, H5N1 Subtype immunology, Kinetics, Madin Darby Canine Kidney Cells, SARS-CoV-2 immunology, Vero Cells, Induced Pluripotent Stem Cells cytology, Influenza A Virus, H5N1 Subtype physiology, Neurons virology, SARS-CoV-2 physiology, Viral Tropism, Virus Replication
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with a wide variety of neurological complications. Even though SARS-CoV-2 is rarely detected in the central nervous system (CNS) or cerebrospinal fluid, evidence is accumulating that SARS-CoV-2 might enter the CNS via the olfactory nerve. However, what happens after SARS-CoV-2 enters the CNS is poorly understood. Therefore, we investigated the replication kinetics, cell tropism, and associated immune responses of SARS-CoV-2 infection in different types of neural cultures derived from human induced pluripotent stem cells (hiPSCs). SARS-CoV-2 was compared to the neurotropic and highly pathogenic H5N1 influenza A virus. SARS-CoV-2 infected a minority of individual mature neurons, without subsequent virus replication and spread, despite angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and neuropilin-1 (NPR1) expression in all cultures. However, this sparse infection did result in the production of type III interferons and interleukin-8 (IL-8). In contrast, H5N1 virus replicated and spread very efficiently in all cell types in all cultures. Taken together, our findings support the hypothesis that neurological complications might result from local immune responses triggered by virus invasion, rather than abundant SARS-CoV-2 replication in the CNS. IMPORTANCE Infections with the recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are often associated with neurological complications. Evidence suggests that SARS-CoV-2 enters the brain via the olfactory nerve; however, SARS-CoV-2 is only rarely detected in the central nervous system of COVID-19 patients. Here, we show that SARS-CoV-2 is able to infect neurons of human iPSC neural cultures but that this infection is abortive and does not result in virus spread to other cells. However, infection of neural cultures did result in the production of type III interferon and IL-8. This study suggests that SARS-CoV-2 might enter the CNS and infect individual neurons, triggering local immune responses that could contribute to the pathogenesis of SARS-CoV-2-associated CNS disease.

Published
2021
Full Text
View/download PDF

24. Conserved UBE3A subcellular distribution between human and mice is facilitated by non-homologous isoforms.

Author

Zampeta FI, Sonzogni M, Niggl E, Lendemeijer B, Smeenk H, de Vrij FMS, Kushner SA, Distel B, and Elgersma Y

Subjects
Alternative Splicing genetics, Angelman Syndrome pathology, Animals, Brain metabolism, Brain pathology, Genomic Imprinting genetics, Humans, Mice, Neurons pathology, Protein Isoforms genetics, Angelman Syndrome genetics, Neurons metabolism, Ubiquitin-Protein Ligases genetics
Abstract

The human UBE3A gene, which is essential for normal neurodevelopment, encodes three Ubiquitin E3 ligase A (UBE3A) protein isoforms. However, the subcellular localization and relative abundance of these human UBE3A isoforms are unknown. We found, as previously reported in mice, that UBE3A is predominantly nuclear in human neurons. However, this conserved subcellular distribution is achieved by strikingly distinct cis-acting mechanisms. A single amino-acid deletion in the N-terminus of human hUBE3A-Iso3, which is homologous to cytosolic mouse mUBE3A-Iso2, results in its translocation to the nucleus. This singe amino-acid deletion is shared with apes and Old World monkeys and was preceded by the appearance of the cytosolic hUBE3A-Iso2 isoform. This hUBE3A-Iso2 isoform arose after the lineage of New World monkeys and Old World monkeys separated from the Tarsiers (Tarsiidae). Due to the loss of a single nucleotide in a non-coding exon, this exon became in frame with the remainder of the UBE3A protein. RNA-seq analysis of human brain samples showed that the human UBE3A isoforms arise by alternative splicing. Consistent with the predominant nuclear enrichment of UBE3A in human neurons, the two nuclear-localized isoforms, hUBE3A-Iso1 and -Iso3, are the most abundantly expressed isoforms of UBE3A, while hUBE3A-Iso2 maintains a small pool of cytosolic UBE3A. Our findings provide new insight into UBE3A localization and evolution and may have important implications for gene therapy approaches in Angelman syndrome., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Published
2020
Full Text
View/download PDF

25. Novel genetic loci affecting facial shape variation in humans.

Author

Xiong Z, Dankova G, Howe LJ, Lee MK, Hysi PG, de Jong MA, Zhu G, Adhikari K, Li D, Li Y, Pan B, Feingold E, Marazita ML, Shaffer JR, McAloney K, Xu SH, Jin L, Wang S, de Vrij FM, Lendemeijer B, Richmond S, Zhurov A, Lewis S, Sharp GC, Paternoster L, Thompson H, Gonzalez-Jose R, Bortolini MC, Canizales-Quinteros S, Gallo C, Poletti G, Bedoya G, Rothhammer F, Uitterlinden AG, Ikram MA, Wolvius E, Kushner SA, Nijsten TE, Palstra RT, Boehringer S, Medland SE, Tang K, Ruiz-Linares A, Martin NG, Spector TD, Stergiakouli E, Weinberg SM, Liu F, and Kayser M

Subjects
Adolescent, Adult, Anatomic Landmarks, Body Patterning genetics, Child, Child, Preschool, Female, Gene Expression Regulation, Developmental genetics, Gene Ontology, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Imaging, Three-Dimensional, Male, Middle Aged, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Young Adult, Face anatomy & histology, Genetic Loci genetics, Maxillofacial Development genetics, Phenotype
Abstract

The human face represents a combined set of highly heritable phenotypes, but knowledge on its genetic architecture remains limited, despite the relevance for various fields. A series of genome-wide association studies on 78 facial shape phenotypes quantified from 3-dimensional facial images of 10,115 Europeans identified 24 genetic loci reaching study-wide suggestive association (p < 5 × 10 -8 ), among which 17 were previously unreported. A follow-up multi-ethnic study in additional 7917 individuals confirmed 10 loci including six unreported ones (p adjusted < 2.1 × 10 -3 ). A global map of derived polygenic face scores assembled facial features in major continental groups consistent with anthropological knowledge. Analyses of epigenomic datasets from cranial neural crest cells revealed abundant cis -regulatory activities at the face-associated genetic loci. Luciferase reporter assays in neural crest progenitor cells highlighted enhancer activities of several face-associated DNA variants. These results substantially advance our understanding of the genetic basis underlying human facial variation and provide candidates for future in-vivo functional studies., Competing Interests: ZX, GD, LH, ML, PH, Md, GZ, KA, DL, YL, BP, EF, MM, JS, KM, SX, LJ, SW, Fd, BL, SR, AZ, SL, GS, LP, HT, RG, MB, SC, CG, GP, GB, FR, AU, MI, EW, SK, TN, RP, SB, SM, KT, AR, NM, TS, ES, SW, FL, MK No competing interests declared, (© 2019, Xiong et al.)

Published
2019
Full Text
View/download PDF

26. A functional variant in the miR-142 promoter modulating its expression and conferring risk of Alzheimer disease.

Author

Ghanbari M, Munshi ST, Ma B, Lendemeijer B, Bansal S, Adams HH, Wang W, Goth K, Slump DE, van den Hout MCGN, van IJcken WFJ, Bellusci S, Pan Q, Erkeland SJ, de Vrij FMS, Kushner SA, and Ikram MA

Subjects
Alleles, Alzheimer Disease metabolism, Animals, Cell Line, Chromosome Mapping, Computational Biology methods, Disease Models, Animal, Gene Expression Regulation, Genetic Association Studies, Genome-Wide Association Study, Hippocampus metabolism, Humans, Induced Pluripotent Stem Cells cytology, Induced Pluripotent Stem Cells metabolism, Mice, Mice, Knockout, Models, Biological, Neural Stem Cells cytology, Neural Stem Cells metabolism, Polymorphism, Single Nucleotide, RNA Interference, RNA, Untranslated, Alzheimer Disease genetics, Genetic Predisposition to Disease, Genetic Variation, MicroRNAs genetics, Promoter Regions, Genetic
Abstract

Noncoding RNAs have been widely recognized as essential mediators of gene regulation. However, in contrast to protein-coding genes, much less is known about the influence of noncoding RNAs on human diseases. Here we examined the association of genetic variants located in primary microRNA sequences and long noncoding RNAs (lncRNAs) with Alzheimer disease (AD) by leveraging data from the largest genome-wide association meta-analysis of late-onset AD. Variants annotated to 5 miRNAs and 10 lncRNAs (in seven distinct loci) exceeded the Bonferroni-corrected significance threshold (p < 1.02 × 10 -6 ). Among these, a leading variant (rs2526377:A>G) at the 17q22 locus annotated to two noncoding RNAs (MIR142 and BZRAP1-AS) was significantly associated with a reduced risk of AD and fulfilled predefined criteria for being a functional variant. Our functional genomic analyses revealed that rs2526377 affects the promoter activity and decreases the expression of miR-142. Moreover, differential expression analysis by RNA-Seq in human iPSC-derived neural progenitor cells and the hippocampus of miR-142 knockout mice demonstrated multiple target genes of miR-142 in the brain that are likely to be involved in the inflammatory and neurodegenerative manifestations of AD. These include TGFBR1 and PICALM, of which their derepression in the brain due to reduced expression levels of miR-142-3p may reduce the risk of AD., (© 2019 Wiley Periodicals, Inc.)

Published
2019
Full Text
View/download PDF

27. Candidate CSPG4 mutations and induced pluripotent stem cell modeling implicate oligodendrocyte progenitor cell dysfunction in familial schizophrenia.

Author

de Vrij FM, Bouwkamp CG, Gunhanlar N, Shpak G, Lendemeijer B, Baghdadi M, Gopalakrishna S, Ghazvini M, Li TM, Quadri M, Olgiati S, Breedveld GJ, Coesmans M, Mientjes E, de Wit T, Verheijen FW, Beverloo HB, Cohen D, Kok RM, Bakker PR, Nijburg A, Spijker AT, Haffmans PMJ, Hoencamp E, Bergink V, Vorstman JA, Wu T, Olde Loohuis LM, Amin N, Langen CD, Hofman A, Hoogendijk WJ, van Duijn CM, Ikram MA, Vernooij MW, Tiemeier H, Uitterlinden AG, Elgersma Y, Distel B, Gribnau J, White T, Bonifati V, and Kushner SA

Subjects
Adult, Antigens genetics, Cell Differentiation physiology, Chondroitin Sulfate Proteoglycans metabolism, Diffusion Tensor Imaging, Family, Female, Humans, Induced Pluripotent Stem Cells metabolism, Male, Membrane Proteins metabolism, Mutation genetics, Oligodendrocyte Precursor Cells physiology, Oligodendroglia metabolism, Pedigree, Proteoglycans genetics, Schizophrenia metabolism, White Matter metabolism, Chondroitin Sulfate Proteoglycans genetics, Membrane Proteins genetics, Oligodendrocyte Precursor Cells metabolism, Schizophrenia genetics
Abstract

Schizophrenia is highly heritable, yet its underlying pathophysiology remains largely unknown. Among the most well-replicated findings in neurobiological studies of schizophrenia are deficits in myelination and white matter integrity; however, direct etiological genetic and cellular evidence has thus far been lacking. Here, we implement a family-based approach for genetic discovery in schizophrenia combined with functional analysis using induced pluripotent stem cells (iPSCs). We observed familial segregation of two rare missense mutations in Chondroitin Sulfate Proteoglycan 4 (CSPG4) (c.391G > A [p.A131T], MAF 7.79 × 10 -5 and c.2702T > G [p.V901G], MAF 2.51 × 10 -3 ). The CSPG4 A131T mutation was absent from the Swedish Schizophrenia Exome Sequencing Study (2536 cases, 2543 controls), while the CSPG4 V901G mutation was nominally enriched in cases (11 cases vs. 3 controls, P = 0.026, OR 3.77, 95% CI 1.05-13.52). CSPG4/NG2 is a hallmark protein of oligodendrocyte progenitor cells (OPCs). iPSC-derived OPCs from CSPG4 A131T mutation carriers exhibited abnormal post-translational processing (P = 0.029), subcellular localization of mutant NG2 (P = 0.007), as well as aberrant cellular morphology (P = 3.0 × 10 -8 ), viability (P = 8.9 × 10 -7 ), and myelination potential (P = 0.038). Moreover, transfection of healthy non-carrier sibling OPCs confirmed a pathogenic effect on cell survival of both the CSPG4 A131T (P = 0.006) and CSPG4 V901G (P = 3.4 × 10 -4 ) mutations. Finally, in vivo diffusion tensor imaging of CSPG4 A131T mutation carriers demonstrated a reduction of brain white matter integrity compared to unaffected sibling and matched general population controls (P = 2.2 × 10 -5 ). Together, our findings provide a convergence of genetic and functional evidence to implicate OPC dysfunction as a candidate pathophysiological mechanism of familial schizophrenia.

Published
2019
Full Text
View/download PDF

28. SOX10 Single Transcription Factor-Based Fast and Efficient Generation of Oligodendrocytes from Human Pluripotent Stem Cells.

Author

García-León JA, Kumar M, Boon R, Chau D, One J, Wolfs E, Eggermont K, Berckmans P, Gunhanlar N, de Vrij F, Lendemeijer B, Pavie B, Corthout N, Kushner SA, Dávila JC, Lambrichts I, Hu WS, and Verfaillie CM

Subjects
Amyotrophic Lateral Sclerosis genetics, Amyotrophic Lateral Sclerosis therapy, Antigens, Surface genetics, Gene Expression Regulation, Developmental, Humans, Multiple Sclerosis genetics, Multiple Sclerosis pathology, Multiple Sclerosis therapy, Myelin Basic Protein genetics, Neurons pathology, Neurons transplantation, Oligodendroglia cytology, Oligodendroglia transplantation, Pluripotent Stem Cells cytology, Pluripotent Stem Cells transplantation, Transcriptome genetics, Cell Differentiation genetics, Oligodendroglia metabolism, Pluripotent Stem Cells metabolism, SOXE Transcription Factors genetics
Abstract

Scarce access to primary samples and lack of efficient protocols to generate oligodendrocytes (OLs) from human pluripotent stem cells (hPSCs) are hampering our understanding of OL biology and the development of novel therapies. Here, we demonstrate that overexpression of the transcription factor SOX10 is sufficient to generate surface antigen O4-positive (O4 + ) and myelin basic protein-positive OLs from hPSCs in only 22 days, including from patients with multiple sclerosis or amyotrophic lateral sclerosis. The SOX10-induced O4 + population resembles primary human OLs at the transcriptome level and can myelinate neurons in vivo. Using in vitro OL-neuron co-cultures, myelination of neurons by OLs can also be demonstrated, which can be adapted to a high-throughput screening format to test the response of pro-myelinating drugs. In conclusion, we provide an approach to generate OLs in a very rapid and efficient manner, which can be used for disease modeling, drug discovery efforts, and potentially for therapeutic OL transplantation., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2018
Full Text
View/download PDF

29. The influence of staffing levels on the use of seclusion.

Author

Janssen W, Noorthoorn E, Linge Rv, and Lendemeijer B

Subjects
Adult, Female, Hospitals, Psychiatric, Humans, Male, Violence prevention & control, Health Facility Environment, Mental Disorders nursing, Organizational Policy, Patient Isolation statistics & numerical data, Personnel Staffing and Scheduling statistics & numerical data
Abstract

This study focussed on the relationship between the use of seclusion and staff characteristics, such as number of nurses on shift, male-female staff ratio, level of education and level of work experience. A retrospective analysis of staff characteristics was applied to administrative data from ten wards in four mid-sized general psychiatric hospitals in the Netherlands. The data show that two variables were associated with seclusion rates: the male-female staff ratio and the variability in team's work experience. More female and less male nurses in a shift and less variability in team's work experience predicted an increase in seclusion rates.

Published
2007
Full Text
View/download PDF

30. The use of seclusion in psychiatry: a literature review.

Author

Lendemeijer B and Shortridge-Baggett L

Subjects
Humans, Patient Advocacy, Terminology as Topic, Mental Disorders nursing, Mental Disorders therapy, Patient Isolation psychology, Patient Isolation statistics & numerical data, Psychiatric Department, Hospital
Abstract

This article reports on a literature review of the practice of seclusion in psychiatric inpatient facilities. Attention is paid to the moral debate on seclusion. Most publications consider seclusion as a necessary intervention to manage problem behavior. The first part of the article deals with definitional aspects leading toward concept clarification. The review shows differences in definitional aspects, motives for seclusion, hospital characteristics, and patient characteristics. Data on frequency, incidence, and duration appear to be widely divergent. The experiences of patients who have been secluded are mostly negative, but positive reactions are also reported. In the publications of the last decade, there is emphasis on the contribution of hospital characteristics to trends in use of seclusion. Finally, it is concluded that seclusion is an effective way to manage (potentially) dangerous behavior and that seclusion is an intervention that may create therapeutic possibilities for care.

Published
1997

31. [Utilization of seclusion. Motives and reasons of nurses].

Author

Lendemeijer B

Subjects
Clinical Nursing Research methods, Crisis Intervention, Motivation, Patient Admission, Mental Disorders nursing, Nursing Staff, Hospital psychology, Patient Isolation, Psychiatric Nursing
Abstract

Seclusion is one of several possible interventions with which patients and health care professionals can be confronted on units for admission and crisis intervention in mental health care institutions. The way in which psychiatric nurses shape their practice with regard to seclusion and how they experience this intervention is unclear. The goal of this study is to describe this practice. The results render insight in the motives and reasons of nurses for use of seclusion, the content of the term emergency situation, the way in which decisions to seclude are taken and which interventions can be labelled as preventive. Finally conclusions are given and the questions raised in this study are discussed.

Published
1997

34. [The use of isolation in psychiatry--a literature study].

Author

Lendemeijer B

Subjects
Adult, Emotions, Female, Humans, Male, Mental Disorders psychology, Terminology as Topic, Dangerous Behavior, Mental Disorders therapy, Patient Isolation
Abstract

This article reports on a literature review into the publications on the practise of seclusion. Attention will be paid to the moral debate on seclusion. The major part of the publications consider seclusion as a necessary intervention to manage problem behaviour. The first part of the article will consider definitional aspects and will result in concept clarification. The review shows differences at definitional aspects, motives for seclusion and patient characteristics. Data on frequencies, incidence and duration appear to be different. The experience of patients who are secluded are mostly negative, but positive reactions are also reported. Publications on the influence of the hospital characteristics to the use of seclusion seem to increase during time. Finally it is concluded that seclusion is an effective way to manage (potential) dangerous behaviour and that seclusion is an intervention which may create therapeutic conditions.

Published
1997

Catalog

Books, media, physical & digital resources
See catalog results