Search

Your search keyword '"A. Zabirnik"' showing total 13 results
Start Over Author "A. Zabirnik"
13 results on '"A. Zabirnik"'

6. The role of LMNA mutations in myogenic differentiation of C2C12 and primary satellite cells

Author

Anna Malashicheva, R. I. Dmitrieva, Anna Kostareva, A. S. Zabirnik, Kseniya Perepelina, and N. A. Smolina

Subjects
0301 basic medicine, 030102 biochemistry & molecular biology, Myogenesis, Cellular differentiation, Cell Biology, Gene mutation, Biology, Cell morphology, Molecular biology, Chromatin, LMNA, 03 medical and health sciences, 030104 developmental biology, Nuclear lamina, Inner membrane
Abstract

Nuclear lamins form nuclear lamina located under the inner nuclear membrane. It was believed that the nuclear lamina plays predominantly a structural role. Recently, its involvement in regulatory processes have been described, e.g., chromatin organization and gene transcription. It is known that mutations in the LMNA gene lead to development of laminopathies, primarily affecting tissues of mesenchymal origin. Today, the mechanisms of the lamina regulation of cell differentiation are largely unknown. In the present work, we studied the effect of LMNA gene mutations on the process of muscle differentiation of primary satellite cells and in С2С12 cell line. The genome of satellite and С2С12 cells was modified by cell transduction via lentiviral constructs encoding LMNA G232E associated with the development of Emery–Dreyfus muscular dystrophy and LMNA R571S associated with the development of dilated cardiomyopathy. Cell morphology was assessed with immunofluorescence, and expression of myogenic genes was analyzed by qPCR. We showed that the analyzed mutations reduced the cell ability to differentiate (to fuse and to form myotubes). We proposed that these mutations enhanced expression of early and reduced expression of late markers of myogenesis. Thus, mutations in nuclear lamins can modify the process of muscle differentiation.

Published
2017

7. THE ROLE OF LMNA MUTATIONS IN MYOGENIC DIFFERENTIATION OF PRIMARY SATELLITE CELLS AND C2C12 CELLS

Author

K I, Perepelina, N A, Smolina, A S, Zabirnik, R I, Dmitrieva, A B, Malashicheva, and A A, Kostareva

Subjects
Male, Mice, Amino Acid Substitution, Satellite Cells, Skeletal Muscle, Mutation, Missense, Animals, Cell Differentiation, Lamin Type A, Muscle Development, Muscular Dystrophy, Emery-Dreifuss, Cell Line
Abstract

Nuclear lamins form nuclear lamina localized under the inner nuclear membrane. It was previously considered that the nuclear lamina predominantly plays a structural role, however, its involvement have been recently described in the regulatory processes such as chromatin organization and gene transcription. It is known that mutations in the LMNA gene lead to the development of a large number of diseases, laminopathies, which mainly affect mesenchymal tissue. Nowadays, the mechanisms by which the lamina can regulate cell differentiation remain incompletely understood. In the present work, we have studied the effect of LMNA gene mutations on the process of muscle differentiation of primary satellite cells and Ñ2Ñ12 cell line. The genome of satellite cells and Ñ2Ñ12 cell line was modified by the introduction of lentiviral constructs encoding LMNA G232E associated with the development of muscular dystrophy Emery—Dreyfus and LMNA R571S associated with the development of dilated cardiomyopathy. The morphology of the cells was estimated using immunofluorescence, the expression level of myogenic genes were analyzed by qPCR. We have shown that the analyzed mutations reduce the ability of cells to differentiate, to fuse and to form myotubes. We have suggested that it is due to enhanced expression of markers at the early stages and to reduced expression markers at the late stages of myogenesis. Therefore, mutations in nuclear lamins can influence the process of muscle differentiation.

Published
2018

8. Nuclear lamins regulate osteogenic differentiation of mesenchymal stem cells

Author

Renata I. Dmitrieva, A. S. Zabirnik, Anna Malashicheva, Elena Ignatieva, Anna Kostareva, A Gudkova, Natalia Smolina, and Maria Bogdanova

Subjects
Genetics, congenital, hereditary, and neonatal diseases and abnormalities, integumentary system, Cellular differentiation, Mesenchymal stem cell, Notch signaling pathway, Cell Biology, Cell fate determination, Biology, Cell biology, LMNA, embryonic structures, Nuclear lamina, Signal transduction, Lamin
Abstract

Nuclear lamins are the major proteins of nuclear envelope and provide the strength of nuclear membrane as well as the interaction of extra-nuclear structures with components of cell nucleus. Recently, it became clear that lamins not only play a structural role in the cell, but could also regulate cell fate, for example lamins could influence cell differentiation via interaction with components of the Notch signaling pathway. Human mutations in LMNA, encoding lamin A/C lead to diseases commonly referred to as laminopathies. Different mutations cause tissue specific phenotypes that affect predominantly a tissue of mesenchymal origin. The nature of this phenomenon, as well as the mechanisms by which lamins regulate cell differentiation remain poorly understood. The aim of this study was to investigate the effect of different mutations of the LMNA on human mesenchymal stem cell (MSC) osteogenic differentiation, and to explore a possible interaction of lamins and Notch signaling pathway. We modified human MSC with mutant LMNA bearing known mutations with tissue specific phenotype associated with different laminopathies. We have shown that mutations associated with different diseases have different effects on the efficiency of MSC osteogenic differentiation and on the expression of specific osteogenic markers SPP1, IBSP and BGLAP. We have also shown that one of the mechanisms involved in the regulation of MSC differentiation may be an interaction of lamins A/C with components of Notch signaling.

Published
2014

9. Lamin A/C mutations alter differentiation potential of mesenchymal stem cells

Author

Renata I. Dmitrieva, A. S. Zabirnik, Anna Malashicheva, Natalia Smolina, and Anna Kostareva

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, Mutation, integumentary system, Point mutation, Mesenchymal stem cell, Adipose tissue, Cell Biology, Gene mutation, Biology, medicine.disease_cause, Molecular biology, Cell biology, LMNA, Adipogenesis, embryonic structures, medicine, Lamin
Abstract

Mutations in the lamin A/C gene (LMNA) lead to severe disorders collectively called laminopathies. The mechanisms by which lamin mutations cause the diseases are not clear. Since the mesenchymal lineages, adipose tissue in particular, are mostly affected in laminopathies, the aim of the study was to estimate the effect of LMNA mutations on differentiation of mesenchymal stem cells, adipose tissue stromal cells (ATSCs), into adipose lineages. ATSCs transduced with lentiviral vectors carrying LMNA gene mutations associated with various syndromes (myodystrophy, cardiomyopathy, lipodystrophy, progeroid syndrome) were induced to adipose differentiate. It was found that introduction of genetic constructions with LMNA gene point mutations G465D, R482L, and R527C promote adipogenic differentiation compared to wild-type lamin gene; mutation R471C reduced the differentiation. Introduction of R471C or R527C lamin mutations profoundly increased the expression of adipogenesis markers PPARG, SREBP1, and adipsin. Mutations in A/C lamin gene strongly and variously affect the differentiation of mesenchymal stem cells that probably underlie the pathogenic changes in patients with laminopathies.

Published
2013

10. Poster session 1

Author

J. Schlueter, T. Brand, D. J. Henderson, V. Boczonadi, P. Humbert, B. Chaudhry, D. Sedmera, J. Svatunkova, R. Kockova, B. Sankova, C. Lopez Sanchez, D. Franco, A. Aranega, V. Garcia-Martinez, E. Demina, V. Miroshikova, A. Denisenko, A. Schwarzman, F. Sanchez-Cabo, C. Torroja, A. Benguria, R. Buchan, P. Srivastava, F. Martinez, P. Barton, S. Cook, A. Dopazo, E. Lara-Pezzi, H. Rai, S. Kumar, A. K. Sharma, S. Mastana, A. Kapoor, C. M. Pandey, S. Agrawal, N. Sinha, J. Lipkova, M. Goldbergova, J. Parenica, J. Bienertova Vasku, A. Vasku, P. Kala, J. Spinar, L. Perez-Cabornero, D. Cantalapiedra, A. Forteza, R. Saez-Villaverde, J. Zumalde, V. Fernandez-Pedrosa, S. Zuniga-Trejos, M. Gil-Borja, M. Lazaro, S. Santillan, M. Costa, N. Cortez-Dias, P. Carrilho-Ferreira, D. Silva, C. Jorge, R. Placido, C. Calisto, M. Fiuza, A. Nunes Diogo, F. J. Enguita, H. H. W. Sillje, B. Lu, H. Yu, M. Zwartbol, W. P. Ruifrok, W. H. Van Gilst, R. A. De Boer, D. Zaliaduonyte-Peksiene, S. Simonyte, V. Lesauskaite, J. Vaskelyte, V. Mizariene, R. Zaliunas, W. Tigchelaar, E. Barlaka, A. Lazou, C. Del Giudice, E. Cipolletta, A. Anastasio, G. Santulli, M. Rusciano, A. S. Maione, P. Campiglia, M. Illario, B. Trimarco, G. Iaccarino, G. A. Frentzou, M. J. Drinkhill, N. A. Turner, S. G. Ball, J. F. X. Ainscough, L. Bertrand, F. Mailleux, J. Hammond, A. Ginion, L. Hue, J. L. Balligand, S. Horman, J. L. Vanoverschelde, C. Beauloye, B. Demeulder, S. L. Puhl, A. Mueller, Y. Devaux, D. R. Wagner, K. Roemer, M. Boehm, C. Maack, D. Miranda-Silva, I. Falcao-Pires, N. Goncalves, D. Moreira-Goncalves, A. F. Leite-Moreira, F. Mraiche, L. Fliegel, J. Xue, G. G. Haddad, L. C. Hsiao, C. Carr, Z. F. Cui, K. Clarke, M. A. D'amico, P. Izzicupo, A. Di Fonso, A. Bascelli, S. Gallina, A. Di Baldassarre, C. Silvestre, P. Fernandez, O. M. Pello, C. Indolfi, F. Civeira, R. Hutter, B. Ibanez, J. Chaves, J. Martinez-Gonzalez, V. Andres Garcia, A. Zabirnik, N. Smolina, A. Malashicheva, E. Omelchenko, T. Sejersen, A. Kostareva, C. Noack, M. P. Zafiriou, A. Renger, R. Dietz, H. J. Schaeffer, M. B. Bergmann, C. Zelarayan, S. Van Linthout, K. Miteva, M. P. Becher, M. Haag, J. Ringe, H.-P. schultheiss, M. Sittinger, C. Tschoepe, T. Kakuchaya, L. Bockeria, E. Golukhova, M. Eremeeva, N. Chigogidze, I. Aslanidi, I. Shurupova, A. Svobodov, A. A. Ramkisoensing, D. A. Pijnappels, J. Swildens, M. J. Goumans, M. J. Schalij, A. A. F. De Vries, D. E. Atsma, A. Gomes, G. M. Costa, C. A. Cordeiro, A. Matsuada, L. B. Rosario, A. P. Freire, M. Bousquenaud, M. Rolland-Turner, F. Maskali, L. Zhang, P. Y. Marie, F. Azuaje, A. J. Smith, G. M. Ellison, C. D. Waring, S. Purushothaman, D. Torella, B. Nadal-Ginard, M. H. Van Marion, D. W. J. Van Der Schaft, M.-J. Goumans, F. P. T. Baaijens, C. V. C. Bouten, N. Kraenkel, K. Kuschnerus, M. Mueller, T. Speer, S. Briand, M. Bader, P. Madeddu, T. F. Luescher, U. Landmesser, A. Papalamprou, C. Vicinanza, D. F. Goldspink, M. Noseda, S. J. Mcsweeney, T. Leja, E. Belian, I. Macaulay, F. Al-Beidh, S. Koenemann, M. S. Abreu Pavia, S. E. Jacobsen, M. D. Schneider, G. Foldes, Z. Bagyura, Z. Lendvai, D. Mathe, T. Nemeth, J. Skopal, I. Foldes, B. Merkely, S. E. Harding, A. J. Candasamy, R. S. Haworth, A. Boguslavsky, F. Cuello, M. J. Shattock, M. Mayr, M. Gautel, M. Avkiran, P. Leszek, B. Sochanowicz, M. Szperl, P. Kolsut, K. Brzoska, W. Piotrowski, T. Rywik, B. Danko, J. Rozanski, M. Kruszewski, N. Bouteldja, R. J. Woodman, C. L. Hewitson, E. Domingo, J. A. Barbara, A. A. Mangoni, R. Carnicer Hijazo, A. B. Hale, X. Liu, S. Suffredini, J. K. Bendall, G. B. S. Lim, N. J. Alp, K. M. Channon, B. Casadei, L. R. Moltzau, J. M. Aronsen, S. Meier, I. Sjaastad, T. Skomedal, J.-B. Osnes, F. O. Levy, E. Qvigstad, P. T. Wright, L. M. K. Pannell, A. R. Lyon, J. Gorelik, A. Guellich, S. F. Vatner, R. Fischmeister, B. Manoury, E. Dubois, J. Hamelet, A. Vanderper, P. Herijgers, D. Langin, F. Gartner, J. Gummert, H. Milting, G. Euler, M. Priess, J. Heger, T. Noll, R. Schulz, T. Doi, T. Akagami, T. Naka, T. Masuyama, M. Ohyanagi, M. Massaro, E. Scoditti, M. Pellegrino, M. A. Carluccio, C. Martines, C. Storelli, R. De Caterina, M. Falck-Hansen, M. E. Goddard, J. E. Cole, N. Astola, A. J. Cross, R. Krams, C. Monaco, M. F. Corsten, W. Verhesen, A. P. Papageorgiou, P. Carai, M. Lindow, S. Obad, G. Summer, L. De Rijck, S. Coort, M. Hazebroek, R. Van Leeuwen, M. Gijbels, M. P. J. De Winther, F. R. M. Stassen, S. Kauppinen, B. Schroen, S. Heymans, Z. Husti, V. Juhasz, L. Virag, A. Kristof, I. Koncz, T. Szel, I. Baczko, N. Jost, J. G. Y. Papp, A. Varro, A. Ghigo, A. Perino, F. Damilano, J. Leroy, V. O. Nikolaev, W. Richter, M. Conti, G. Vandecasteele, E. Hirsch, R. Ang, S. Sebastian, A. Ludwig, L. Birnbaumer, A. Tinker, E. A. Ertel, R. Sube, A. Opel, C. L-H Huang, A. Grace, N. Tribulova, J. Radosinska, B. Bacova, T. Benova, V. Knezl, J. Slezak, T. A. Matsuyama, T. Tanaka, T. Adachi, Y. Jiang, H. Ishibashi-Ueda, T. Takamatsu, J. Kornej, C. Reihardt, J. Kosiuk, A. Arya, G. Hindricks, V. Adams, D. Husser, A. Bollmann, S. Severi, M. Fantini, E. Ravagli, L. A. Charawi, D. Difrancesco, C. Poulet, L. Lu, U. R. Ravens, M. Hoch, T. Koenig, A. Gardiwal, B. Stapel, S. Erschow, A. Froese, B. Weinhold, R. Gerardy-Schahn, G. Klein, D. Hilfiker-Kleiner, K. Chinda, S. Palee, S. Surinkaew, M. Phornphutkul, S. Chattipakorn, N. Chattipakorn, B. Tuana, Z. Kohajda, A. A. Kristof, C. Corici, F. Fulop, N. L. Jost, V. Szuts, D. Menesi, G. L. Puskas, A. Zvara, N. Houshmand, J. G. Papp, N. Al-Shanti, M. Hancock, A. Venturini, C. Stewart, R. Ascione, G. Angelini, M.-S. Suleiman, A. Gonzalez-Tendero, I. Torre, F. Crispi, E. Gratacos, T. Tzanavari, E. Varela, A. Economides, S. Theocharis, C. Pantos, D. V. Cokkinos, A. Karalis, P. Hecker, V. Lionetti, W. C. Stanley, C. Ferrara, N. Piroddi, B. Scellini, C. Ferrantini, V. Sequiera, C. Remedios, L. Carrier, C. Tesi, J. Van Der Velden, C. Poggesi, V. Kooij, G. J. M. Stienen, D. Dooijes, s. Marston, C. Redwood, C. Dos Remedios, I. Diakonov, S. Tokar, M. Sikkel, S. Schlossarek, M. Sauer, A. Papageorgiou, S. Velthuis, E. Lutgens, M. Swinnen, N. Van Rooijen, J. Kzhyshkowska, P. Carmeliet, P. Garcia-Canadilla, F. Garcia-Garcia, I. Iruretagoiena, J. Dopazo, I. Amat-Roldan, M. H. Zhang, Y. H. Zhang, C. E. Sears, B. Wojtas, A. Llach, L. Hove-Madsen, V. Spinelli, L. Sartiani, M. Bucciantini, R. Coppini, E. Russo, A. Mugelli, E. Cerbai, M. Stefani, M. Ibrahim, P. Kukadia, M. Navaratnarajah, U. Siedlecka, C. Van Doorn, M. Yacoub, C. Terracciano, W. Song, N. Curtin, R. Woledge, S. Marston, M. Balteau, N. Tajeddine, G. Behets-Wydemans, C. Dessy, P. Gailly, W. J. Van Der Laarse, S. J. P. Bogaards, D. Van Groen, Y. Y. Wong, I. Schalij, A. Vonk Noordegraaf, F. M. Faz, B. Littlejohns, P. Pasdois, A. P. Halestrap, G. D. Angelini, S. Lemoine, V. Jaspard-Vinassa, F. Vigneron, P. Dos Santos, M. Popescu, A. Vlad, G. Isvoranu, L. Suciu, B. Marinescu, D. Dimulescu, L. Zagrean, P. W. M. Kleikers, K. Wingler, K. Radermacher, A. Sydykov, H. A. Ghofrani, N. Weissmann, H. H. W. Schmidt, A. Poddubnaya, K. E. M. Khurs, S. O. G. Smolenskaya, G. Szucs, Z. Murlasits, S. Torok, G. F. Kocsis, T. Csont, C. Csonka, P. Ferdinandy, R. Dongworth, D. M. Yellon, D. J. Hausenloy, Y. Y. Chen, W. S. Lian, C. F. Cheng, K. H. Khoo, T. C. Meng, G. Youcef, E. Belaidi, L. Fazal, M. P. Vinvent, D. De Paulis, G. Zadigue, C. Richer-Giudicelli, F. Alhenc-Gelas, M. Ovize, A. Pizard, R. Cal, J. Castellano, J. Farre, G. Vilahur, L. Badimon, V. Llorente-Cortes, H. Naz, M. Gharanei, C. Mee, H. Maddock, A. Hussain, O. Pisarenko, V. Shulzhenko, L. Serebryakova, I. Studneva, Y. Pelogeykina, D. Khatri, O. Tskitishvili, E. Barnucz, G. Veres, P. Hegedus, T. Radovits, S. Korkmaz, S. Klein, R. Zoller, M. Karck, G. Szabo, S. Morel, M. A. Frias, C. Rosker, R. W. James, S. Rohr, B. R. Kwak, V. Braunersreuther, B. Foglia, F. Mach, E. Shantsila, S. Montoro-Garcia, L. D. Tapp, S. Apostolakis, B. J. Wrigley, G. Y. H. Lip, E. Sokolowska, K. Przyborowski, K. Kramkowski, W. Buczko, A. Mogielnicki, U. Simonsen, E. R. Hedegaard, B. D. Nielsen, A. Kun, A. Hughes, C. Kroigaard, S. Mogensen, O. Frobert, K. Ait Aissa, J. P. Max, D. Wahl, T. Lecompte, P. Lacolley, V. Regnault, A. Novakovic, M. Pavlovic, A. Vranic, P. Milojevic, I. Stojanovic, M. Jovic, D. Nenezic, N. Ugresic, Q. Yang, G. W. He, L. Calvier, P. Reboul, B. Martin-Fernandez, V. Lahera, F. Zannad, V. Cachofeiro, P. Rossignol, N. Lopez-Andres, V. K. Pulakazhi Venu, R. Baetta, A. Bonomo, A. F. Muro, A. Corsini, A. L. Catapano, G. D. Norata, L. E. Viiri, L. E. Full, T. J. Navin, A. Didangelos, I. Seppala, T. Lehtimaki, A. H. Davies, R. Wait, D. Sedding, P. Stieger, C. Thoelen, S. Fischer, J. M. Daniel, R. Widmer-Teske, K. T. Preissner, N. Alenina, L. A. Rabelo, M. Todiras, V. N. Souza, J. M. Penninger, R. A. Santos, I. A. Leonova, S. A. Boldueva, V. S. Feoktistova, O. V. Sirotkina, M. G. Kolesnichenko, Z. Springo, P. Toth, P. Cseplo, G. Szijjarto, A. Koller, S. Puthenkalam, M. K. Frey, I. M. Lang, R. Madonna, H. Shelat, Y. J. Geng, T. Ziegler, V. Pfetsch, J. Horstkotte, C. Schwab, I. Rohwedde, R. Hinkel, Q. Di, S. Dietzel, U. Deutsch, C. Kupatt, I. Ernens, B. Lenoir, O. Fortunato, A. Caporali, E. Sangalli, D. Cordella, M. Marchetti, G. Spinetti, C. Emanueli, G. Arderiu, E. Pena, M. J. Forteza, V. Bodi, S. Novella, C. Alguero, I. Trapero, I. Benet, C. Hermenegildo, J. Sanchis, F. J. Chorro, A. Nemeth, S. Szabados, A. Cziraki, E. Sulyok, I. G. Horvath, M. Rauh, W. Rascher, I. Sikharulidze, I. B. Bakhlishvili, J. T. T. Laitinen, J. P. Hytonen, O. Leppanen, J. Taavitsainen, A. Partanen, P. Korpisalo, S. Yla-Herttuala, J. Lonn, J. Hallstrom, T. Bengtsson, M. C. Guisasola, E. Dulin, S. Stojkovic, C. Kaun, G. Maurer, K. Huber, J. Wojta, S. Demyanets, T. B. Opstad, A. Pettersen, S. Aakra, H. Arnesen, I. Seljeflot, M. Borrell-Pages, C. Romero, A. Toso, M. Leoncini, L. Tanini, T. Pizzetti, F. Tropeano, M. Maioli, P. Casprini, F. Bellandi, R. F. Antunes, J. C. Kaski, I. E. Dumitriu, E. Wu, A. A. L. Tareen, M. Udovychenko, I. Rudyk, K. Riches, L. Franklin, A. Maqbool, J. Bond, M. L. Koschinsky, D. J. O'regan, K. E. Porter, I. R. Parepa, A. I. Suceveanu, A. Suceveanu, L. Mazilu, L. Cojocaru, A. Rusali, L. A. Tuta, E. Craiu, D. Lindner, C. Zietsch, H.-P. Schultheiss, C. Tschope, D. Westermann, M. Miana, E. Martinez, R. Jurado, C. Delgado, N. Gomez-Hurtado, A. Briones, J. Young, T. J. Geng, A. Brodehl, T. Schmidt, O. Smolenskaya, C. Stegemann, D. Byzov, I. Mikhaylova, N. Chizh, E. Pushkova, O. Synchykova, B. Sandomirsky, O. Freylikhman, O. Rotar, N. Chromova, E. Moguchaya, V. Ivanenko, E. Kolesova, A. Erina, M. Boyarinova, A. Konradi, S. D. Preston, D. Baskaran, A. M. Plonczak, K. Norita, S. V. De Noronha, M. N. Sheppard, A. Haghikia, S. F. Hill, M. Hoepfner, B. Nitzsche, M. Schrader, F. Zengerling, B. Hoffmann, A. Pries, S. Gao, J. T. Laitinen, S. Laidinen, H. Markkanen, H. Karvinen, V. Marjomaki, I. Vajanto, T. T. Rissanen, K. Alitalo, P. Mello Ferrao, M. C. Waghabi, L. R. Garzoni, J. Ritterhoff, C. Weidenhammer, M. Voelkers, W. H. Zimmermann, J. Rabinowitz, P. Most, S. C. Gordts, I. Muthuramu, F. Jacobs, E. Van Craeyveld, E. Nefyodova, B. De Geest, D. R. Tribuddharat, D. R. Sathitkarnmanee, M. R. Buddhisa, M. S. Suwannasaen, D. R. Silarat, D. R. Ngamsangsirisup, D. R. Hawrylowicz, D. R. Lertmemongkolchai, S. Rain, M. L. Handoko, N. Westerhof, A. Vonk-Noordegraaf, F. S. De Man, A. S. Iakovleva, O. A. Mirolyubova, A. Berezin, T. A. Samura, Suwannasaen, Tippayawat, Ngamsangsirisup, D. R. Sutra, Hawrylowicz, Lertmemongkolchai, L. M. Lima, M. G. Carvalho, D. R. G. Junqueira, M. O. Sousa, A. Zampetaki, P. Willeit, L. Tilling, I. Drozdov, M. Prokopi, A. Shah, C. Boulanger, P. Chowienczyk, S. Kiechl, S. H. V. Oliveira, V. Kirillova, E. Prosviryakov, C. T. M. Van Der Pouw Kraan, F. J. P. Bernink, J. M. Baggen, L. Timmers, A. M. Beek, M. Diamant, A. C. Van Rossum, N. Van Royen, A. J. G. Horrevoets, J. E. A. Appelman, A. Zyatenkov, L. S. Kokov, Y. U. D. Volynskiy, M. Krestjyaninov, V. I. Ruzov, A. V. Villar, E. Martinez-Laorden, A. Almela, M. A. Hurle, M. L. Laorden, N. Apaijai, M. K. Mcmullen, J. M. Whitehouse, G. Shine, and A. Towell

Subjects
Gerontology, Physiology, business.industry, Physiology (medical), Cancer research, Medicine, SCRIB gene, Cardiology and Cardiovascular Medicine, business
Published
2012

11. [Lamin A/C mutations change differentiation potential of mesenchymal stem cells]

Author

Ab, Malashicheva, As, Zabirnik, Na, Smolina, Ea, Omel Chenko, Renata Dmitrieva, and Aa, Kostareva

Subjects
Adipose Tissue, Mutation, Humans, Cell Differentiation, Cell Lineage, Mesenchymal Stem Cells, Lamin Type A
Abstract

Mutations in lamin A/C gene (LMNA) lead to development of severe disorders--laminopathies. Unlike most other types of intermediate filaments, where the pathological effect of mutations is tightly linked to alteration of mechanical and integrative functions, the detailed mechanism of lamin mutations is still unclear and possibly involves the alteration of nuclear signaling and transcriptional processes. Since the mesenchymal lineage tissues such as myocardium, skeletal muscle, adipose and bone tissues are mostly affected in laminopathies, the role of lamin A/C in differentiation process of mesenchymal stem cells has been assumed. The aim of the study was to estimate the effect of LMNA mutations of differentiation of mesenchymal stem cells into adipose lineages. In vitro mitagenesis was performed on wild type LMNA gene incorporated in a lentiviral vector. Several previously described mutations in LMNA were used, each associated with a certain phenotype. Adipose-derived mesenchymal stem cells from healthy donors were transduced with lentiviruses bearing either wild-type or mutant LMNA. Cells were then induced to adipose differentiation. We show that mutant LMNA/C promotes differentiation capacity of mesenchymal stem cells as seen by morphological changes and by expression of specific adipose markers.

12. [Nuclear lamins regulate osteogenic differentiation of mesenchymal stem cells]

Author

Ma, Bogdanova, Gudkova AIa, As, Zabirnik, Ev, Ignat Eva, Renata Dmitrieva, Na, Smolina, Aa, Kostareva, and Ab, Malashicheva

Subjects
Cell Nucleus, Osteoblasts, Receptors, Notch, Transcription, Genetic, Osteocalcin, Primary Cell Culture, Cell Cycle Proteins, Cell Differentiation, Mesenchymal Stem Cells, Lamin Type A, Gene Expression Regulation, Mutation, Basic Helix-Loop-Helix Transcription Factors, Humans, Integrin-Binding Sialoprotein, Osteopontin, Biomarkers, Signal Transduction
Abstract

Nuclear lamins are the major proteins of nuclear envelope and provide the strength of nuclear membrane as well as the interaction of extra-nuclear structures with components of cell nucleus. Recently, it became clear that lamins not only play a structural role in the cell, but could also regulate cell fate, for example lamins could influence cell differentiation via interaction with components of the Notch signaling pathway. Human mutations in LMNA, encoding lamin A/C lead to diseases commonly referred to as laminopathies. Different mutations cause tissue specific phenotypes that affect predominantly a tissue of mesenchymal origin. The nature of this phenomenon, as well as the mechanisms by which lamins regulate cell differentiation remain poorly understood. The aim of this study was to investigate the effect of different mutations of the LMNA on human mesenchymal stem cell (MSC) osteogenic differentiation, and to explore a possible interaction of lamins and Notch signaling pathway. We modified human MSC with mutant LMNA bearing known mutations with tissue specific phenotype associated with different laminopathies. We have shown that mutations associated with different diseases have different effects on the efficiency of MSC osteogenic differentiation and on the expression of specific osteogenic markers SPP1, IBSP and BGLAP. We have also shown that one of the mechanisms involved in the regulation of MSC differentiation may be an interaction of lamins A/C with components of Notch signaling.

Catalog

Books, media, physical & digital resources
See catalog results