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1. Alternative platelet differentiation pathways initiated by nonhierarchically related hematopoietic stem cells

Author

Carrelha, Joana, Mazzi, Stefania, Winroth, Axel, Hagemann-Jensen, Michael, Ziegenhain, Christoph, Högstrand, Kari, Seki, Masafumi, Brennan, Margs S., Lehander, Madeleine, Wu, Bishan, Meng, Yiran, Markljung, Ellen, Norfo, Ruggiero, Ishida, Hisashi, Belander Strålin, Karin, Grasso, Francesca, Simoglou Karali, Christina, Aliouat, Affaf, Hillen, Amy, Chari, Edwin, Siletti, Kimberly, Thongjuea, Supat, Mead, Adam J., Linnarsson, Sten, Nerlov, Claus, Sandberg, Rickard, Yoshizato, Tetsuichi, Woll, Petter S., and Jacobsen, Sten Eirik W.

Published
2024
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2. Single-cell multi-omics identifies chronic inflammation as a driver of TP53-mutant leukemic evolution

Author

Rodriguez-Meira, Alba, Norfo, Ruggiero, Wen, Sean, Chédeville, Agathe L., Rahman, Haseeb, O’Sullivan, Jennifer, Wang, Guanlin, Louka, Eleni, Kretzschmar, Warren W., Paterson, Aimee, Brierley, Charlotte, Martin, Jean-Edouard, Demeule, Caroline, Bashton, Matthew, Sousos, Nikolaos, Moralli, Daniela, Subha Meem, Lamia, Carrelha, Joana, Wu, Bishan, Hamblin, Angela, Guermouche, Helene, Pasquier, Florence, Marzac, Christophe, Girodon, François, Vainchenker, William, Drummond, Mark, Harrison, Claire, Chapman, J. Ross, Plo, Isabelle, Jacobsen, Sten Eirik W., Psaila, Bethan, Thongjuea, Supat, Antony-Debré, Iléana, and Mead, Adam J.

Published
2023
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4. Constructing custom-made radiotranscriptomic signatures of vascular inflammation from routine CT angiograms: a prospective outcomes validation study in COVID-19

Author

Ahern, David J, Ai, Zhichao, Ainsworth, Mark, Allan, Chris, Allcock, Alice, Angus, Brian, Ansari, M Azim, Arancibia-Cárcamo, Carolina, Aschenbrenner, Dominik, Attar, Moustafa, Baillie, J Kenneth, Barnes, Eleanor, Bashford-Rogers, Rachael, Bashyal, Archana, Beer, Sally, Berridge, Georgina, Beveridge, Amy, Bibi, Sagida, Bicanic, Tihana, Blackwell, Luke, Bowness, Paul, Brent, Andrew, Brown, Andrew, Broxholme, John, Buck, David, Burnham, Katie, Byrne, Helen, Camara, Susana, Ferreira, Ivan Candido, Charles, Philip, Chen, Wentao, Chen, Yi-Ling, Chong, Amanda, Clutterbuck, Elizabeth, Coles, Mark, Conlon, Christopher, Cornall, Richard, Cribbs, Adam, Curion, Fabiola, Davenport, Emma, Davidson, Neil, Davis, Simon, Dendrou, Calliope, Dequaire, Julie, Dib, Lea, Docker, James, Dold, Christina, Dong, Tao, Downes, Damien, Drakesmith, Hal, Dunachie, Susanna, Duncan, David, Eijsbouts, Chris, Esnouf, Robert, Espinosa, Alexis, Etherington, Rachel, Fairfax, Benjamin, Fairhead, Rory, Fang, Hai, Fassih, Shayan, Felle, Sally, Fernandez Mendoza, Maria, Ferreira, Ricardo, Fischer, Roman, Foord, Thomas, Forrow, Aden, Frater, John, Fries, Anastasia, Gallardo Sanchez, Veronica, Garner, Lucy, Geeves, Clementine, Georgiou, Dominique, Godfrey, Leila, Golubchik, Tanya, Gomez Vazquez, Maria, Green, Angie, Harper, Hong, Harrington, Heather, Heilig, Raphael, Hester, Svenja, Hill, Jennifer, Hinds, Charles, Hird, Clare, Ho, Ling-Pei, Hoekzema, Renee, Hollis, Benjamin, Hughes, Jim, Hutton, Paula, Jackson-Wood, Matthew, Jainarayanan, Ashwin, James-Bott, Anna, Jansen, Kathrin, Jeffery, Katie, Jones, Elizabeth, Jostins, Luke, Kerr, Georgina, Kim, David, Klenerman, Paul, Knight, Julian, Kumar, Vinod, Kumar Sharma, Piyush, Kurupati, Prathiba, Kwok, Andrew, Lee, Angela, Linder, Aline, Lockett, Teresa, Lonie, Lorne, Lopopolo, Maria, Lukoseviciute, Martyna, Luo, Jian, Marinou, Spyridoula, Marsden, Brian, Martinez, Jose, Matthews, Philippa, Mazurczyk, Michalina, McGowan, Simon, McKechnie, Stuart, Mead, Adam, Mentzer, Alexander, Mi, Yuxin, Monaco, Claudia, Montadon, Ruddy, Napolitani, Giorgio, Nassiri, Isar, Novak, Alex, O'Brien, Darragh, O'Connor, Daniel, O'Donnell, Denise, Ogg, Graham, Overend, Lauren, Park, Inhye, Pavord, Ian, Peng, Yanchun, Penkava, Frank, Pereira Pinho, Mariana, Perez, Elena, Pollard, Andrew, Powrie, Fiona, Psaila, Bethan, Quan, T Phuong, Repapi, Emmanouela, Revale, Santiago, Silva-Reyes, Laura, Richard, Jean-Baptiste, Rich-Griffin, Charlotte, Ritter, Thomas, Rollier, Christine, Rowland, Matthew, Ruehle, Fabian, Salio, Mariolina, Sansom, Stephen Nicholas, Sanches Peres, Raphael, Santos Delgado, Alberto, Sauka-Spengler, Tatjana, Schwessinger, Ron, Scozzafava, Giuseppe, Screaton, Gavin, Seigal, Anna, Semple, Malcolm, Sergeant, Martin, Simoglou Karali, Christina, Sims, David, Skelly, Donal, Slawinski, Hubert, Sobrinodiaz, Alberto, Sousos, Nikolaos, Stafford, Lizzie, Stockdale, Lisa, Strickland, Marie, Sumray, Otto, Sun, Bo, Taylor, Chelsea, Taylor, Stephen, Taylor, Adan, Thongjuea, Supat, Thraves, Hannah, Todd, John, Tomic, Adriana, Tong, Orion, Trebes, Amy, Trzupek, Dominik, Tucci, Felicia Anna, Turtle, Lance, Udalova, Irina, Uhlig, Holm, van Grinsven, Erinke, Vendrell, Iolanda, Verheul, Marije, Voda, Alexandru, Wang, Guanlin, Wang, Lihui, Wang, Dapeng, Watkinson, Peter, Watson, Robert, Weinberger, Michael, Whalley, Justin, Witty, Lorna, Wray, Katherine, Xue, Luzheng, Yuen Yeung, Hing, Yin, Zixi, Young, Rebecca, Youngs, Jonathan, Zhang, Ping, Zurke, Yasemin-Xiomara, Banning, Adrian, Antonopoulos, Alexios, Bajaj, Amrita, Kelion, Andrew, Deshpande, Aparna, Kardos, Attila, Hudson, Benjamin, Koo, Bon-Kwon, Shirodaria, Cheerag, Xie, Cheng, Kotanidis, Christos, Mahon, Ciara, Berry, Colin, Adlam, David, Newby, David, Connolly, Derek, Scaletta, Diane, Alexander, Donna, Nicol, Ed, McAlindon, Elisa, Oikonomou, Evangelos, Pugliese, Francesca, Pontone, Gianluca, Benedetti, Giulia, He, Guo-Wei, West, Henry, Kondo, Hidekazu, Benedek, Imre, Das, Intrajeet, Deanfield, John, Graby, John, Greenwood, John, Rodrigues, Jonathan, Ge, Junbo, Channon, Keith, Fabritz, Larissa, Fan, Li-Juan, Kingham, Lucy, Guglielmo, Marco, Lyasheva, Maria, Schmitt, Matthias, Beer, Meinrad, Anderson, Michelle, Desai, Milind, Marwan, Mohamed, Takahashi, Naohiko, Mehta, Nehal, Dai, Neng, Screaton, Nicholas, Sabharwal, Nikant, Maurovich-Horvat, Pál, Rao, Praveen, Kotronias, Rafail, Kharbanda, Rajesh, Preston, Rebecca, Wood, Richard, Blankstein, Ron, Rajani, Ronak, Mirsadraee, Saeed, Munir, Shahzad, Thomas, Sheena, Neubauer, Stefan, Klömpken, Steffen, Petersen, Steffen, Achenbach, Stephan, Anthony, Susan, Mak, Sze, Mittal, Tarun, Benedek, Theodora, Sharma, Vinoda, Lin, Wen-Hua, Kotanidis, Christos P, Rodrigues, Jonathan C L, O’Connor, Daniel, Siddique, Muhammad, Lockstone, Helen, Oikonomou, Evangelos K, Badi, Ileana, Lumley, Sheila F, Constantinides, Bede, Sanderson, Nicholas, Rodger, Gillian, Chau, Kevin K, Lodge, Archie, Tsakok, Maria, Gleeson, Fergus, Indrajeet, Das, Hudson, Benjamin J, Srivastava, Vivek, Farid, Shakil, Krasopoulos, George, Sayeed, Rana, Newby, David E, Channon, Keith M, and Antoniades, Charalambos

Published
2022
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5. CD34+CD19−CD22+ B-cell progenitors may underlie phenotypic escape in patients treated with CD19-directed therapies

Author

Bueno, Clara, Barrera, Susana, Bataller, Alex, Ortiz-Maldonado, Valentín, Elliot, Natalina, O'Byrne, Sorcha, Wang, Guanlin, Rovira, Montse, Gutierrez-Agüera, Francisco, Trincado, Juan L., González-González, María, Morgades, Mireia, Sorigué, Marc, Bárcena, Paloma, Zanetti, Samanta Romina, Torrebadell, Montse, Vega-Garcia, Nerea, Rives, Susana, Mallo, Mar, Sole, Francesc, Mead, Adam J., Roberts, Irene, Thongjuea, Supat, Psaila, Bethan, Juan, Manel, Delgado, Julio, Urbano-Ispizúa, Alvaro, Ribera, Josep María, Orfao, Alberto, Roy, Anindita, and Menendez, Pablo

Published
2022
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6. Hematopoietic stem cell heterogeneity and age-associated platelet bias are evolutionarily conserved.

Author

Aksöz, Merve, Gafencu, Grigore-Aristide, Stoilova, Bilyana, Buono, Mario, Zhang, Ying, Turkalj, Sven, Meng, Yiran, Jakobsen, Niels Asger, Metzner, Marlen, Clark, Sally-Ann, Beveridge, Ryan, Thongjuea, Supat, Vyas, Paresh, and Nerlov, Claus

Subjects
HEMATOPOIETIC stem cells, BLOOD cells, RNA sequencing, BONE marrow, HEMATOPOIESIS
Abstract

Hematopoietic stem cells (HSCs) reconstitute multilineage human hematopoiesis after clinical bone marrow (BM) transplantation and are the cells of origin of some hematological malignancies. Although HSCs provide multilineage engraftment, individual murine HSCs are lineage biased and contribute unequally to blood cell lineages. Here, we performed high-throughput single-cell RNA sequencing in mice after xenograft with molecularly barcoded adult human BM HSCs. We demonstrated that human individual BM HSCs are also functionally and transcriptionally lineage biased. Specifically, we identified platelet-biased and multilineage human HSCs. Quantitative comparison of transcriptomes from single HSCs from young and aged BM showed that both the proportion of platelet-biased HSCs and their level of transcriptional platelet priming increase with age. Therefore, platelet-biased HSCs and their increased prevalence and transcriptional platelet priming during aging are conserved features of mammalian evolution. Editor's summary: Hematopoietic stem cells (HSCs) are required for blood cell production throughout life. Murine HSCs can be biased toward the megakaryocyte/platelet lineage, but whether platelet-biased human HSCs exist remains to be determined. Aksöz et al. combined molecular barcoding and single-cell RNA sequencing to track the fate of human HSCs (hHSCs) in vivo. After xenograft into mice, a population of bone marrow hHSCs was platelet biased, and the prevalence of platelet-biased hHSCs increased with HSC age. This work demonstrates that age-associated HSC platelet bias is evolutionarily conserved. —Hannah Isles [ABSTRACT FROM AUTHOR]

Published
2024
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7. Gene regulatory network landscape of Group 3/4 medulloblastoma

Author

Joshi, Piyush, primary, Stelzer, Tamina, additional, Okonechnikov, Konstantin, additional, Sarropoulos, Ioannis, additional, Sepp, Mari, additional, Pour-Jamnani, Mischan V., additional, Rademacher, Anne, additional, Yamada-Saito, Tetsuya, additional, Schneider, Céline, additional, Schmidt, Julia, additional, Schäfer, Philipp, additional, Leiss, Kevin, additional, Bortolomeazzi, Michele, additional, Mallm, Jan-Philipp, additional, da Silva, Patricia B.G., additional, Statz, Britta, additional, Wittmann, Andrea, additional, Schramm, Kathrin, additional, Blattner-Johnson, Mirjam, additional, Fiesel, Petra, additional, Jones, Barbara, additional, Milde, Till, additional, Pajtler, Kristian, additional, van Tilburg, Cornelis M., additional, Witt, Olaf, additional, Rippe, Karsten, additional, Korshunov, Andrey, additional, Jones, David T.W., additional, Hovestadt, Volker, additional, Northcott, Paul A., additional, Thongjuea, Supat, additional, Jäger, Natalie, additional, Kaessmann, Henrik, additional, Pfister, Stefan M., additional, and Kutscher, Lena M., additional

Published
2024
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9. Chromothripsis orchestrates leukemic transformation in blast phase MPN through targetable amplification of DYRK1A

Author

Brierley, Charlotte K, primary, Yip, Bon Ham, additional, Orlando, Giulia, additional, Goyal, Harsh, additional, Wen, Sean, additional, Wen, Jeremy, additional, Levine, Max F, additional, Jakobsdottir, Maria G, additional, Rodriguez-Meira, Alba, additional, Adamo, Assunta, additional, Bashton, Matthew, additional, Hamblin, Angela, additional, Clark, Sally A, additional, O'Sullivan, Jennifer, additional, Murphi, Lauren, additional, Olijnik-French, Aude-Anais, additional, Cotton, Anitria, additional, Narina, Shilpa, additional, Pruett-Miller, Shondra, additional, Enshaei, Amir, additional, Harrison, Claire, additional, Drummond, Mark, additional, Knapper, Stephen, additional, Tefferi, Ajalew, additional, Antony-Debre, Ileana, additional, Thongjuea, Supat, additional, Wedge, David C, additional, Constantinescu, Stefan, additional, Papaemmanuil, Elli, additional, Psaila, Bethan, additional, Crispino, John D, additional, and Mead, Adam J, additional

Published
2023
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11. A pro-inflammatory stem cell niche drives myelofibrosis through a targetable galectin 1 axis

Author

Li, Rong, primary, Colombo, Michela, additional, Wang, Guanlin, additional, Rodriguez-Romera, Antonio, additional, O'Sullivan, Jennifer, additional, Clark, Sally-Ann, additional, Pérez Sáez, Juan, additional, Meng, Yiran, additional, Khan, Abdullah, additional, Wen, Sean, additional, Dong, Pengwei, additional, Zhou, Wenjiang, additional, Sousos, Nikolaos, additional, Murphy, Lauren, additional, Clarke, Matthew, additional, Jooss, Natalie, additional, Olijnik, Aude-Anais, additional, Wong, Zoe, additional, Sirinukunwattana, Korsuk, additional, Ryou, Hosuk, additional, Norfo, Ruggiero, additional, Cheng, Qian, additional, Brierley, Charlotte, additional, Carrelha, Joana, additional, Ren, Zemin, additional, Thongjuea, Supat, additional, Rathinam, Vijay, additional, Krishnan, Anandi Krishnan, additional, Royston, Daniel, additional, Rabinovich, Gabriel, additional, Mead, Adam, additional, and Psaila, Bethan, additional

Published
2023
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12. P332: LIN28B: AN IMPORTANT ONCO-FETAL GENE IN INFANT ACUTE LYMPHOBLASTIC LEUKAEMIA

Author

Ling, Rebecca, primary, Jackson, Thomas, additional, Elliott, Natalina, additional, Cross, Joe, additional, Rice, Siobhan, additional, Howitt, Rebecca, additional, Smith, Alastair, additional, Harman, Joe, additional, T Crump, Nicholas, additional, Wang, Guanlin, additional, Iskander, Deena, additional, Thongjuea, Supat, additional, Ancliff, Philip, additional, Psaila, Beth, additional, Roberts, Irene, additional, Milne, Thomas, additional, and Roy, Anindita, additional

Published
2023
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14. 3031 – CHROMOTHRIPSIS AND LEUKEMIC TRANSFORMATION IN MPN

Author

Brierley, Charlotte, primary, Yip, Bon Ham, additional, Orlando, Giulia, additional, Goyal, Harsh, additional, Wen, Sean, additional, Wen, Jeremy, additional, Levine, Max, additional, Rodriguez-Meira, Alba, additional, Adamo, Assunta, additional, Bashton, Matthew, additional, Hamblin, Angela, additional, Clark, Sally Ann, additional, Fletcher, Rachel, additional, Fox, Sonia, additional, Gaskell, Charlotte, additional, O'Sullivan, Jennifer, additional, Murphy, Lauren, additional, Sousos, Nikolaos, additional, Enshai, Amir, additional, Harrison, Claire, additional, Drummond, Mark, additional, Knapper, Steven, additional, Antony-Debre, Ileana, additional, Thongjuea, Supat, additional, Constantinescu, Stefan, additional, Papaemmanuil, Elli, additional, Psaila, Bethan, additional, Crispino, John, additional, and Mead, Adam, additional

Published
2023
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16. Cross-Talk between Hematopoietic Cells and Fibroblast Subsets Drives Inflammation and Remodelling of the Bone Marrow Microenvironment in Myeloproliferative Neoplasms

Author

Li, Rong, primary, Colombo, Michela, additional, Wang, Guanlin, additional, Clark, Sally-Ann, additional, Rodriguez-Romera, Antonio, additional, Meng, Yiran, additional, Khan, Abdullah, additional, Wen, Wei Xiong, additional, Sousos, Nikolaos, additional, Murphy, Lauren, additional, Simoglou Karali, Christina, additional, Sirinukunwattana, Korsuk, additional, O'Sullivan, Jennifer, additional, Norfo, Ruggiero, additional, Cheng, Qian, additional, Brierley, Charlotte, additional, Carrelha, Joana, additional, Ren, Zemin, additional, Rabinovich, Gabriel A., additional, Rathinam, Vijay A, additional, Thongjuea, Supat, additional, Royston, Daniel, additional, Mead, Adam J, additional, and Psaila, Bethan, additional

Published
2022
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18. Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia

Author

Giustacchini, Alice, Thongjuea, Supat, Barkas, Nikolaos, Woll, Petter S, Povinelli, Benjamin J, Booth, Christopher A G, Sopp, Paul, Norfo, Ruggiero, Rodriguez-Meira, Alba, Ashley, Neil, Jamieson, Lauren, Vyas, Paresh, Anderson, Kristina, Segerstolpe, Åsa, Qian, Hong, Olsson-Strömberg, Ulla, Mustjoki, Satu, Sandberg, Rickard, Jacobsen, Sten Eirik W, and Mead, Adam J

Subjects
RNA sequencing -- Research, Stem cells -- Research, Chronic myeloid leukemia -- Analysis -- Health aspects -- Genetic aspects -- Diagnosis, Biological sciences, Health
Abstract

Recent advances in single-cell transcriptomics are ideally placed to unravel intratumoral heterogeneity and selective resistance of cancer stem cell (SC) subpopulations to molecularly targeted cancer therapies. However, current single-cell RNA-sequencing approaches lack the sensitivity required to reliably detect somatic mutations. We developed a method that combines high-sensitivity mutation detection with whole-transcriptome analysis of the same single cell. We applied this technique to analyze more than 2,000 SCs from patients with chronic myeloid leukemia (CML) throughout the disease course, revealing heterogeneity of CML-SCs, including the identification of a subgroup of CML-SCs with a distinct molecular signature that selectively persisted during prolonged therapy. Analysis of nonleukemic SCs from patients with CML also provided new insights into cell-extrinsic disruption of hematopoiesis in CML associated with clinical outcome. Furthermore, we used this single-cell approach to identify a blast-crisis-specific SC population, which was also present in a subclone of CML-SCs during the chronic phase in a patient who subsequently developed blast crisis. This approach, which might be broadly applied to any malignancy, illustrates how single-cell analysis can identify subpopulations of therapy-resistant SCs that are not apparent through cell-population analysis., Author(s): Alice Giustacchini [1, 2]; Supat Thongjuea [1, 2]; Nikolaos Barkas [1, 2]; Petter S Woll [2]; Benjamin J Povinelli [1, 2]; Christopher A G Booth [1, 2]; Paul Sopp [...]

Published
2017
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19. Constructing custom-made radiotranscriptomic signatures of vascular inflammation from routine CT angiograms: a prospective outcomes validation study in COVID-19

Author

Kotanidis, Christos P, primary, Xie, Cheng, additional, Alexander, Donna, additional, Rodrigues, Jonathan C L, additional, Burnham, Katie, additional, Mentzer, Alexander, additional, O’Connor, Daniel, additional, Knight, Julian, additional, Siddique, Muhammad, additional, Lockstone, Helen, additional, Thomas, Sheena, additional, Kotronias, Rafail, additional, Oikonomou, Evangelos K, additional, Badi, Ileana, additional, Lyasheva, Maria, additional, Shirodaria, Cheerag, additional, Lumley, Sheila F, additional, Constantinides, Bede, additional, Sanderson, Nicholas, additional, Rodger, Gillian, additional, Chau, Kevin K, additional, Lodge, Archie, additional, Tsakok, Maria, additional, Gleeson, Fergus, additional, Adlam, David, additional, Rao, Praveen, additional, Indrajeet, Das, additional, Deshpande, Aparna, additional, Bajaj, Amrita, additional, Hudson, Benjamin J, additional, Srivastava, Vivek, additional, Farid, Shakil, additional, Krasopoulos, George, additional, Sayeed, Rana, additional, Ho, Ling-Pei, additional, Neubauer, Stefan, additional, Newby, David E, additional, Channon, Keith M, additional, Deanfield, John, additional, Antoniades, Charalambos, additional, Ahern, David J, additional, Ai, Zhichao, additional, Ainsworth, Mark, additional, Allan, Chris, additional, Allcock, Alice, additional, Angus, Brian, additional, Ansari, M Azim, additional, Arancibia-Cárcamo, Carolina, additional, Aschenbrenner, Dominik, additional, Attar, Moustafa, additional, Baillie, J Kenneth, additional, Barnes, Eleanor, additional, Bashford-Rogers, Rachael, additional, Bashyal, Archana, additional, Beer, Sally, additional, Berridge, Georgina, additional, Beveridge, Amy, additional, Bibi, Sagida, additional, Bicanic, Tihana, additional, Blackwell, Luke, additional, Bowness, Paul, additional, Brent, Andrew, additional, Brown, Andrew, additional, Broxholme, John, additional, Buck, David, additional, Byrne, Helen, additional, Camara, Susana, additional, Ferreira, Ivan Candido, additional, Charles, Philip, additional, Chen, Wentao, additional, Chen, Yi-Ling, additional, Chong, Amanda, additional, Clutterbuck, Elizabeth, additional, Coles, Mark, additional, Conlon, Christopher, additional, Cornall, Richard, additional, Cribbs, Adam, additional, Curion, Fabiola, additional, Davenport, Emma, additional, Davidson, Neil, additional, Davis, Simon, additional, Dendrou, Calliope, additional, Dequaire, Julie, additional, Dib, Lea, additional, Docker, James, additional, Dold, Christina, additional, Dong, Tao, additional, Downes, Damien, additional, Drakesmith, Hal, additional, Dunachie, Susanna, additional, Duncan, David, additional, Eijsbouts, Chris, additional, Esnouf, Robert, additional, Espinosa, Alexis, additional, Etherington, Rachel, additional, Fairfax, Benjamin, additional, Fairhead, Rory, additional, Fang, Hai, additional, Fassih, Shayan, additional, Felle, Sally, additional, Fernandez Mendoza, Maria, additional, Ferreira, Ricardo, additional, Fischer, Roman, additional, Foord, Thomas, additional, Forrow, Aden, additional, Frater, John, additional, Fries, Anastasia, additional, Gallardo Sanchez, Veronica, additional, Garner, Lucy, additional, Geeves, Clementine, additional, Georgiou, Dominique, additional, Godfrey, Leila, additional, Golubchik, Tanya, additional, Gomez Vazquez, Maria, additional, Green, Angie, additional, Harper, Hong, additional, Harrington, Heather, additional, Heilig, Raphael, additional, Hester, Svenja, additional, Hill, Jennifer, additional, Hinds, Charles, additional, Hird, Clare, additional, Hoekzema, Renee, additional, Hollis, Benjamin, additional, Hughes, Jim, additional, Hutton, Paula, additional, Jackson-Wood, Matthew, additional, Jainarayanan, Ashwin, additional, James-Bott, Anna, additional, Jansen, Kathrin, additional, Jeffery, Katie, additional, Jones, Elizabeth, additional, Jostins, Luke, additional, Kerr, Georgina, additional, Kim, David, additional, Klenerman, Paul, additional, Kumar, Vinod, additional, Kumar Sharma, Piyush, additional, Kurupati, Prathiba, additional, Kwok, Andrew, additional, Lee, Angela, additional, Linder, Aline, additional, Lockett, Teresa, additional, Lonie, Lorne, additional, Lopopolo, Maria, additional, Lukoseviciute, Martyna, additional, Luo, Jian, additional, Marinou, Spyridoula, additional, Marsden, Brian, additional, Martinez, Jose, additional, Matthews, Philippa, additional, Mazurczyk, Michalina, additional, McGowan, Simon, additional, McKechnie, Stuart, additional, Mead, Adam, additional, Mi, Yuxin, additional, Monaco, Claudia, additional, Montadon, Ruddy, additional, Napolitani, Giorgio, additional, Nassiri, Isar, additional, Novak, Alex, additional, O'Brien, Darragh, additional, O'Connor, Daniel, additional, O'Donnell, Denise, additional, Ogg, Graham, additional, Overend, Lauren, additional, Park, Inhye, additional, Pavord, Ian, additional, Peng, Yanchun, additional, Penkava, Frank, additional, Pereira Pinho, Mariana, additional, Perez, Elena, additional, Pollard, Andrew, additional, Powrie, Fiona, additional, Psaila, Bethan, additional, Quan, T Phuong, additional, Repapi, Emmanouela, additional, Revale, Santiago, additional, Silva-Reyes, Laura, additional, Richard, Jean-Baptiste, additional, Rich-Griffin, Charlotte, additional, Ritter, Thomas, additional, Rollier, Christine, additional, Rowland, Matthew, additional, Ruehle, Fabian, additional, Salio, Mariolina, additional, Sansom, Stephen Nicholas, additional, Sanches Peres, Raphael, additional, Santos Delgado, Alberto, additional, Sauka-Spengler, Tatjana, additional, Schwessinger, Ron, additional, Scozzafava, Giuseppe, additional, Screaton, Gavin, additional, Seigal, Anna, additional, Semple, Malcolm, additional, Sergeant, Martin, additional, Simoglou Karali, Christina, additional, Sims, David, additional, Skelly, Donal, additional, Slawinski, Hubert, additional, Sobrinodiaz, Alberto, additional, Sousos, Nikolaos, additional, Stafford, Lizzie, additional, Stockdale, Lisa, additional, Strickland, Marie, additional, Sumray, Otto, additional, Sun, Bo, additional, Taylor, Chelsea, additional, Taylor, Stephen, additional, Taylor, Adan, additional, Thongjuea, Supat, additional, Thraves, Hannah, additional, Todd, John, additional, Tomic, Adriana, additional, Tong, Orion, additional, Trebes, Amy, additional, Trzupek, Dominik, additional, Tucci, Felicia Anna, additional, Turtle, Lance, additional, Udalova, Irina, additional, Uhlig, Holm, additional, van Grinsven, Erinke, additional, Vendrell, Iolanda, additional, Verheul, Marije, additional, Voda, Alexandru, additional, Wang, Guanlin, additional, Wang, Lihui, additional, Wang, Dapeng, additional, Watkinson, Peter, additional, Watson, Robert, additional, Weinberger, Michael, additional, Whalley, Justin, additional, Witty, Lorna, additional, Wray, Katherine, additional, Xue, Luzheng, additional, Yuen Yeung, Hing, additional, Yin, Zixi, additional, Young, Rebecca, additional, Youngs, Jonathan, additional, Zhang, Ping, additional, Zurke, Yasemin-Xiomara, additional, Banning, Adrian, additional, Antonopoulos, Alexios, additional, Kelion, Andrew, additional, Kardos, Attila, additional, Hudson, Benjamin, additional, Koo, Bon-Kwon, additional, Kotanidis, Christos, additional, Mahon, Ciara, additional, Berry, Colin, additional, Newby, David, additional, Connolly, Derek, additional, Scaletta, Diane, additional, Nicol, Ed, additional, McAlindon, Elisa, additional, Oikonomou, Evangelos, additional, Pugliese, Francesca, additional, Pontone, Gianluca, additional, Benedetti, Giulia, additional, He, Guo-Wei, additional, West, Henry, additional, Kondo, Hidekazu, additional, Benedek, Imre, additional, Das, Intrajeet, additional, Graby, John, additional, Greenwood, John, additional, Rodrigues, Jonathan, additional, Ge, Junbo, additional, Channon, Keith, additional, Fabritz, Larissa, additional, Fan, Li-Juan, additional, Kingham, Lucy, additional, Guglielmo, Marco, additional, Schmitt, Matthias, additional, Beer, Meinrad, additional, Anderson, Michelle, additional, Desai, Milind, additional, Marwan, Mohamed, additional, Takahashi, Naohiko, additional, Mehta, Nehal, additional, Dai, Neng, additional, Screaton, Nicholas, additional, Sabharwal, Nikant, additional, Maurovich-Horvat, Pál, additional, Kharbanda, Rajesh, additional, Preston, Rebecca, additional, Wood, Richard, additional, Blankstein, Ron, additional, Rajani, Ronak, additional, Mirsadraee, Saeed, additional, Munir, Shahzad, additional, Klömpken, Steffen, additional, Petersen, Steffen, additional, Achenbach, Stephan, additional, Anthony, Susan, additional, Mak, Sze, additional, Mittal, Tarun, additional, Benedek, Theodora, additional, Sharma, Vinoda, additional, and Lin, Wen-Hua, additional

Published
2022
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21. Deep sequencing of short capped RNAs reveals novel families of noncoding RNAs

Author

de Hoon, Michiel, primary, Bonetti, Alessandro, additional, Plessy, Charles, additional, Ando, Yoshinari, additional, Hon, Chung-Chau, additional, Ishizu, Yuri, additional, Itoh, Masayoshi, additional, Kato, Sachi, additional, Lin, Dongyan, additional, Maekawa, Sho, additional, Murata, Mitsuyoshi, additional, Nishiyori, Hiromi, additional, Shin, Jay W., additional, Stolte, Jens, additional, Suzuki, Ana Maria, additional, Tagami, Michihira, additional, Takahashi, Hazuki, additional, Thongjuea, Supat, additional, Forrest, Alistair R.R., additional, Hayashizaki, Yoshihide, additional, Kere, Juha, additional, and Carninci, Piero, additional

Published
2022
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25. CD34+CD19−CD22+ B-cell progenitors may underlie phenotypic escape in patients treated with CD19-directed therapies

Author

European Research Council, European Commission, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, Cancer Research UK, Wellcome Trust, Generalitat de Catalunya, University of Oxford, Bueno, Clara, Barrera, Susana, Bataller, Alex, Ortiz-Maldonado, Valentín, Elliot, Natalina, O’Byrne, Sorcha, Wang, Guanlin, Rovira, Montserrat, Gutierrez-Aguera, Francisco, Trincado, Juan L., González-González, María, Morgades, Mireia, Sorigué, Marc, Bárcena, Paloma, Zanetti, Samanta Romina, Torrebadell, Montse, Vega-García, Nerea, Rives, Susana, Mallo, Mar, Solé, Francesc, Mead, Adam J., Roberts, Irene, Thongjuea, Supat, Psaila, Bethan, Juan, Manel, Delgado, Julio, Urbano-Ispizúa, Álvaro, Ribera, Josep-Maria, Orfao, Alberto, Roy, Anindita, Menéndez, Pablo, European Research Council, European Commission, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, Cancer Research UK, Wellcome Trust, Generalitat de Catalunya, University of Oxford, Bueno, Clara, Barrera, Susana, Bataller, Alex, Ortiz-Maldonado, Valentín, Elliot, Natalina, O’Byrne, Sorcha, Wang, Guanlin, Rovira, Montserrat, Gutierrez-Aguera, Francisco, Trincado, Juan L., González-González, María, Morgades, Mireia, Sorigué, Marc, Bárcena, Paloma, Zanetti, Samanta Romina, Torrebadell, Montse, Vega-García, Nerea, Rives, Susana, Mallo, Mar, Solé, Francesc, Mead, Adam J., Roberts, Irene, Thongjuea, Supat, Psaila, Bethan, Juan, Manel, Delgado, Julio, Urbano-Ispizúa, Álvaro, Ribera, Josep-Maria, Orfao, Alberto, Roy, Anindita, and Menéndez, Pablo

Abstract

CD19-directed immunotherapies have revolutionized the treatment of advanced B-cell acute lymphoblastic leukemia (B-ALL). Despite initial impressive rates of complete remission (CR) many patients ultimately relapse. Patients with B-ALL successfully treated with CD19-directed T cells eventually relapse, which, coupled with the early onset of CD22 expression during B-cell development, suggests that preexisting CD34+CD22+CD19− (pre)-leukemic cells represent an “early progenitor origin-related” mechanism underlying phenotypic escape to CD19-directed immunotherapies. We demonstrate that CD22 expression precedes CD19 expression during B-cell development. CD34+CD19−CD22+ cells are found in diagnostic and relapsed bone marrow samples of ∼70% of patients with B-ALL, and their frequency increases twofold in patients with B-ALL in CR after CD19 CAR T-cell therapy. The median of CD34+CD19−CD22+ cells before treatment was threefold higher in patients in whom B-ALL relapsed after CD19-directed immunotherapy (median follow-up, 24 months). Fluorescence in situ hybridization analysis in flow-sorted cell populations and xenograft modeling revealed that CD34+CD19−CD22+ cells harbor the genetic abnormalities present at diagnosis and initiate leukemogenesis in vivo. Our data suggest that preleukemic CD34+CD19−CD22+ progenitors underlie phenotypic escape after CD19-directed immunotherapies and reinforce ongoing clinical studies aimed at CD19/CD22 dual targeting as a strategy for reducing CD19− relapses. The implementation of CD34/CD19/CD22 immunophenotyping in clinical laboratories for initial diagnosis and subsequent monitoring of patients with B-ALL during CD19-targeted therapy is encouraged.

Published
2022

27. Deciphering TP53 mutant Cancer Evolution with Single-Cell Multi-Omics

Author

Rodriguez-Meira, Alba, primary, Norfo, Ruggiero, additional, Wen, Wei Xiong, additional, Chédeville, Agathe L., additional, Rahman, Haseeb, additional, O’Sullivan, Jennifer, additional, Wang, Guanlin, additional, Louka, Eleni, additional, Kretzschmar, Warren W., additional, Paterson, Aimee, additional, Brierley, Charlotte, additional, Martin, Jean-Edouard, additional, Demeule, Caroline, additional, Bashton, Matthew, additional, Sousos, Nikolaos, additional, Hamblin, Angela, additional, Guermouche, Helene, additional, Pasquier, Florence, additional, Marzac, Christophe, additional, Girodon, François, additional, Drummond, Mark, additional, Harrison, Claire, additional, Plo, Isabelle, additional, Jacobsen, Sten Eirik W., additional, Psaila, Bethan, additional, Thongjuea, Supat, additional, Antony-Debré, Iléana, additional, and Mead, Adam J, additional

Published
2022
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28. A blood atlas of COVID-19 defines hallmarks of disease severity and specificity

Author

Ahern, David J., primary, Ai, Zhichao, additional, Ainsworth, Mark, additional, Allan, Chris, additional, Allcock, Alice, additional, Angus, Brian, additional, Ansari, M. Azim, additional, Arancibia-Cárcamo, Carolina V., additional, Aschenbrenner, Dominik, additional, Attar, Moustafa, additional, Baillie, J. Kenneth, additional, Barnes, Eleanor, additional, Bashford-Rogers, Rachael, additional, Bashyal, Archana, additional, Beer, Sally, additional, Berridge, Georgina, additional, Beveridge, Amy, additional, Bibi, Sagida, additional, Bicanic, Tihana, additional, Blackwell, Luke, additional, Bowness, Paul, additional, Brent, Andrew, additional, Brown, Andrew, additional, Broxholme, John, additional, Buck, David, additional, Burnham, Katie L., additional, Byrne, Helen, additional, Camara, Susana, additional, Candido Ferreira, Ivan, additional, Charles, Philip, additional, Chen, Wentao, additional, Chen, Yi-Ling, additional, Chong, Amanda, additional, Clutterbuck, Elizabeth A., additional, Coles, Mark, additional, Conlon, Christopher P., additional, Cornall, Richard, additional, Cribbs, Adam P., additional, Curion, Fabiola, additional, Davenport, Emma E., additional, Davidson, Neil, additional, Davis, Simon, additional, Dendrou, Calliope A., additional, Dequaire, Julie, additional, Dib, Lea, additional, Docker, James, additional, Dold, Christina, additional, Dong, Tao, additional, Downes, Damien, additional, Drakesmith, Hal, additional, Dunachie, Susanna J., additional, Duncan, David A., additional, Eijsbouts, Chris, additional, Esnouf, Robert, additional, Espinosa, Alexis, additional, Etherington, Rachel, additional, Fairfax, Benjamin, additional, Fairhead, Rory, additional, Fang, Hai, additional, Fassih, Shayan, additional, Felle, Sally, additional, Fernandez Mendoza, Maria, additional, Ferreira, Ricardo, additional, Fischer, Roman, additional, Foord, Thomas, additional, Forrow, Aden, additional, Frater, John, additional, Fries, Anastasia, additional, Gallardo Sanchez, Veronica, additional, Garner, Lucy C., additional, Geeves, Clementine, additional, Georgiou, Dominique, additional, Godfrey, Leila, additional, Golubchik, Tanya, additional, Gomez Vazquez, Maria, additional, Green, Angie, additional, Harper, Hong, additional, Harrington, Heather A., additional, Heilig, Raphael, additional, Hester, Svenja, additional, Hill, Jennifer, additional, Hinds, Charles, additional, Hird, Clare, additional, Ho, Ling-Pei, additional, Hoekzema, Renee, additional, Hollis, Benjamin, additional, Hughes, Jim, additional, Hutton, Paula, additional, Jackson-Wood, Matthew A., additional, Jainarayanan, Ashwin, additional, James-Bott, Anna, additional, Jansen, Kathrin, additional, Jeffery, Katie, additional, Jones, Elizabeth, additional, Jostins, Luke, additional, Kerr, Georgina, additional, Kim, David, additional, Klenerman, Paul, additional, Knight, Julian C., additional, Kumar, Vinod, additional, Kumar Sharma, Piyush, additional, Kurupati, Prathiba, additional, Kwok, Andrew, additional, Lee, Angela, additional, Linder, Aline, additional, Lockett, Teresa, additional, Lonie, Lorne, additional, Lopopolo, Maria, additional, Lukoseviciute, Martyna, additional, Luo, Jian, additional, Marinou, Spyridoula, additional, Marsden, Brian, additional, Martinez, Jose, additional, Matthews, Philippa C., additional, Mazurczyk, Michalina, additional, McGowan, Simon, additional, McKechnie, Stuart, additional, Mead, Adam, additional, Mentzer, Alexander J., additional, Mi, Yuxin, additional, Monaco, Claudia, additional, Montadon, Ruddy, additional, Napolitani, Giorgio, additional, Nassiri, Isar, additional, Novak, Alex, additional, O'Brien, Darragh P., additional, O'Connor, Daniel, additional, O'Donnell, Denise, additional, Ogg, Graham, additional, Overend, Lauren, additional, Park, Inhye, additional, Pavord, Ian, additional, Peng, Yanchun, additional, Penkava, Frank, additional, Pereira Pinho, Mariana, additional, Perez, Elena, additional, Pollard, Andrew J., additional, Powrie, Fiona, additional, Psaila, Bethan, additional, Quan, T. Phuong, additional, Repapi, Emmanouela, additional, Revale, Santiago, additional, Silva-Reyes, Laura, additional, Richard, Jean-Baptiste, additional, Rich-Griffin, Charlotte, additional, Ritter, Thomas, additional, Rollier, Christine S., additional, Rowland, Matthew, additional, Ruehle, Fabian, additional, Salio, Mariolina, additional, Sansom, Stephen Nicholas, additional, Sanches Peres, Raphael, additional, Santos Delgado, Alberto, additional, Sauka-Spengler, Tatjana, additional, Schwessinger, Ron, additional, Scozzafava, Giuseppe, additional, Screaton, Gavin, additional, Seigal, Anna, additional, Semple, Malcolm G., additional, Sergeant, Martin, additional, Simoglou Karali, Christina, additional, Sims, David, additional, Skelly, Donal, additional, Slawinski, Hubert, additional, Sobrinodiaz, Alberto, additional, Sousos, Nikolaos, additional, Stafford, Lizzie, additional, Stockdale, Lisa, additional, Strickland, Marie, additional, Sumray, Otto, additional, Sun, Bo, additional, Taylor, Chelsea, additional, Taylor, Stephen, additional, Taylor, Adan, additional, Thongjuea, Supat, additional, Thraves, Hannah, additional, Todd, John A., additional, Tomic, Adriana, additional, Tong, Orion, additional, Trebes, Amy, additional, Trzupek, Dominik, additional, Tucci, Felicia Anna, additional, Turtle, Lance, additional, Udalova, Irina, additional, Uhlig, Holm, additional, van Grinsven, Erinke, additional, Vendrell, Iolanda, additional, Verheul, Marije, additional, Voda, Alexandru, additional, Wang, Guanlin, additional, Wang, Lihui, additional, Wang, Dapeng, additional, Watkinson, Peter, additional, Watson, Robert, additional, Weinberger, Michael, additional, Whalley, Justin, additional, Witty, Lorna, additional, Wray, Katherine, additional, Xue, Luzheng, additional, Yeung, Hing Yuen, additional, Yin, Zixi, additional, Young, Rebecca K., additional, Youngs, Jonathan, additional, Zhang, Ping, additional, and Zurke, Yasemin-Xiomara, additional

Published
2022
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29. Identification and Age-dependent Increase of Platelet Biased Human Hematopoietic Stem Cells

Author

Aksoz, Merve, primary, Gafencu, Grigore-Aristide, additional, Stoilova, Bilyana Stoilova, additional, Buono, Mario, additional, Meng, Yiran, additional, Jakobsen, Niels Asger, additional, Metzner, Marlen, additional, Clark, Sally-Ann, additional, Beveridge, Ryan, additional, Thongjuea, Supat, additional, Vyas, Paresh, additional, and Nerlov, Claus, additional

Published
2022
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30. 3170 – SINGLE-CELL MULTI-OMICS RESOLVES THE EVOLUTION OF TP53-MUTANT LEUKEMIA

Author

Rodriguez-Meira, Alba, primary, Norfo, Ruggiero, additional, Wen, Wei, additional, Chedeville, Agathe, additional, Rahman, Haseeb, additional, O'Sullivan, Jennifer, additional, Wang, Guanlin, additional, Louka, Eleni, additional, Kretzschmar, Warren, additional, Paterson, Aimee, additional, Brierley, Charlotte, additional, Martin, Jean-Edouard, additional, Demeule, Caroline, additional, Bashton, Matthew, additional, Sousos, Nikolaos, additional, Hamblin, Angela, additional, Guermouche, Helene, additional, Pasquier, Florence, additional, Marzac, Christophe, additional, Girodon, François, additional, Drummond, Mark, additional, Harrison, Claire, additional, Plo, Isabelle, additional, Jacobsen, Sten Eirik, additional, Psaila, Bethan, additional, Thongjuea, Supat, additional, Antony-Debré, Iléana, additional, and Mead, Adam, additional

Published
2022
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32. 3135 – CD34+CD19-CD22+ B-CELL PROGENITORS MIGHT UNDERLIE PHENOTYPIC ESCAPE IN PATIENTS TREATED WITH CD19-DIRECTED THERAPIES

Author

Menendez, Pablo, primary, Bueno, Clara, additional, Barrera, Susana, additional, Bataller, Alex, additional, Ortiz-Maldonado, Valentín, additional, Elliot, Natalina, additional, O'Byrne, Sorcha, additional, Wang, Gualing, additional, Rovira, Montse, additional, Gutierrez-Agüera, Francisco, additional, Trincado, Juan, additional, Gonzalez-Gonzalez, María, additional, Morgades, Mireia, additional, Sorigue, Marc, additional, Barcena, Paloma, additional, Zanetti, Samanta, additional, Torrebadell, Montse, additional, Vega, Nerea, additional, Rives, Susana, additional, Mallo, Mar, additional, Sole, Francesc, additional, Mead, Adam, additional, Roberts, Irene, additional, Thongjuea, Supat, additional, Psaila, Bethan, additional, Juan, Manel, additional, Delgado, Julio, additional, Urbano-Ispizúa, Alvaro, additional, Ribera, Jose, additional, Orfao, Alberto, additional, Roy, Anindita, additional, and Menendez, Pablo, additional

Published
2022
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33. Single-Cell Multi-Omics Reveals the Genetic, Cellular and Molecular Landscape of TP53 Mutated Leukemic Transformation in MPN

Author

Rodriguez-Meira, Alba, primary, Rahman, Haseeb, additional, Norfo, Ruggiero, additional, Wen, Wei, additional, Chédeville, Agathe, additional, O'Sullivan, Jennifer, additional, Wang, Guanlin, additional, Paterson, Aimee, additional, Louka, Eleni, additional, Brierley, Charlotte K, additional, Kretzschmar, Warren W, additional, Girodon, Francois, additional, Ren, Zemin, additional, Bashton, Matthew, additional, Enshaei, Amir, additional, Drummond, Mark W., additional, Pasquier, Florence, additional, Marzac, Christophe, additional, Harrison, Claire N., additional, Plo, Isabelle, additional, Jacobsen, Sten Eirik W, additional, Thongjuea, Supat, additional, Psaila, Bethan, additional, Antony-Debre, Ileana, additional, and Mead, Adam J., additional

Published
2021
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34. HBS1L-MYB intergenic variants modulate fetal hemoglobin via long-range MYB enhancers

Author

Stadhouders, Ralph, Aktuna, Suleyman, Thongjuea, Supat, Aghajanirefah, Ali, Pourfarzad, Farzin, van IJcken, Wilfred, Lenhard, Boris, Rooks, Helen, Best, Steve, Menzel, Stephan, Grosveld, Frank, Thein, Swee Lay, and Soler, Eric

Subjects
Sickle cell anemia -- Development and progression -- Genetic aspects -- Research, Genetic variation -- Research, Proto-oncogenes -- Research, Fetal hemoglobin -- Genetic aspects -- Physiological aspects -- Research, Health care industry
Abstract

Genetic studies have identified common variants within the intergenic region (HBS1L-MYB) between GTP-binding elongation factor HBS1L and myeloblastosis oncogene MYB on chromosome 6q that are associated with elevated fetal hemoglobin (HbF) levels and alterations of other clinically important human erythroid traits. It is unclear how these noncoding sequence variants affect multiple erythrocyte characteristics. Here, we determined that several HBS1L-MYB intergenic variants affect regulatory elements that are occupied by key erythroid transcription factors within this region. These elements interact with MYB, a critical regulator of erythroid development and HbF levels. We found that several HBS1L-MYB intergenic variants reduce transcription factor binding, affecting long-range interactions with MYB and MYB expression levels. These data provide a functional explanation for the genetic association of HBS1L-MYB intergenic polymorphisms with human erythroid traits and HbF levels. Our results further designate MYB as a target for therapeutic induction of HbF to ameliorate sickle cell and P-thalassemia disease severity., Introduction Approximately half of our blood volume is made up of erythrocytes, providing the oxygen and carbon dioxide transport necessary for cellular respiration throughout the body. Erythroid parameters (e.g., red [...]

Published
2014
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36. Single-cell profiling of human bone marrow progenitors reveals mechanisms of failing erythropoiesis in Diamond-Blackfan anemia

Author

Iskander, Deena, primary, Wang, Guanlin, additional, Heuston, Elisabeth F., additional, Christodoulidou, Chrysi, additional, Psaila, Bethan, additional, Ponnusamy, Kanagaraju, additional, Ren, Hongwei, additional, Mokhtari, Zeinab, additional, Robinson, Mark, additional, Chaidos, Aristeidis, additional, Trivedi, Pritesh, additional, Trasanidis, Nikolaos, additional, Katsarou, Alexia, additional, Szydlo, Richard, additional, Palii, Carmen G., additional, Zaidi, Mehmood H., additional, Al-Oqaily, Qais, additional, Caputo, Valentina S., additional, Roy, Anindita, additional, Harrington, Yvonne, additional, Karnik, Leena, additional, Naresh, Kikkeri, additional, Mead, Adam J., additional, Thongjuea, Supat, additional, Brand, Marjorie, additional, de la Fuente, Josu, additional, Bodine, David M., additional, Roberts, Irene, additional, and Karadimitris, Anastasios, additional

Published
2021
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37. Transitions in lineage specification and gene regulatory networks in hematopoietic stem/progenitor cells over human development

Author

Roy, Anindita, primary, Wang, Guanlin, additional, Iskander, Deena, additional, O’Byrne, Sorcha, additional, Elliott, Natalina, additional, O’Sullivan, Jennifer, additional, Buck, Gemma, additional, Heuston, Elisabeth F., additional, Wen, Wei Xiong, additional, Meira, Alba Rodriguez, additional, Hua, Peng, additional, Karadimitris, Anastasios, additional, Mead, Adam J., additional, Bodine, David M., additional, Roberts, Irene, additional, Psaila, Bethan, additional, and Thongjuea, Supat, additional

Published
2021
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38. Platelet-biased stem cells reside at the apex of the haematopoietic stem-cell hierarchy

Author

Sanjuan-Pla, Alejandra, Macaulay, Iain C., Jensen, Christina T., Woll, Petter S., Luis, Tiago C., Mead, Adam, Moore, Susan, Carella, Cintia, Matsuoka, Sahoko, Jones, Tiphaine Bouriez, Chowdhury, Onima, Stenson, Laura, Lutteropp, Michael, Green, Joanna C.A., Facchini, Raffaella, Boukarabila, Hanane, Grover, Amit, Gambardella, Adriana, Thongjuea, Supat, Carrelha, Joana, Tarrant, Paul, Atkinson, Deborah, Clark, Sally-Ann, Nerlov, Claus, and Jacobsen, Sten Eirik W.

Subjects
Hematopoiesis -- Physiological aspects -- Genetic aspects -- Research, Hematopoietic stem cells -- Physiological aspects -- Research, Blood platelets -- Physiological aspects -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The blood system is maintained by a small pool of haematopoietic stem cells (HSCs), which are required and sufficient for replenishing all human blood cell lineages at millions of cells per second throughout life. Megakaryocytes in the bone marrow are responsible for the continuous production of platelets in the blood, crucial for preventing bleeding--a common and life-threatening side effect of many cancer therapies--and major efforts are focused at identifying the most suitable cellular and molecular targets to enhance platelet production after bone marrow transplantation or chemotherapy (1). Although it has become clear that distinct HSC subsets exist that are stably biased towards the generation of lymphoid or myeloid blood cells (2-4), we are yet to learn whether other types of lineage-biased HSC exist or understand their inter-relationships and how differently lineage-biased HSCs are generated and maintained. The functional relevance of notable phenotypic and molecular similarities between megakaryocytes and bone marrow cells with an HSC cell-surface phenotype (5-8) remains unclear. Here we identify and prospectively isolate a molecularly and functionally distinct mouse HSC subset primed for platelet-specific gene expression, with enhanced propensity for short- and long-term reconstitution of platelets. Maintenance of platelet-biased HSCs crucially depends on thrombopoietin, the primary extrinsic regulator of platelet development (9). Platelet-primed HSCs also frequently have a long-term myeloid lineage bias, can self-renew and give rise to lymphoid-biased HSCs. These findings show that HSC subtypes can be organized into a cellular hierarchy, with platelet-primed HSCs at the apex. They also demonstrate that molecular and functional priming for platelet development initiates already in a distinct HSC population. The identification of a platelet-primed HSC population should enable the rational design of therapies enhancing platelet output., One of the megakaryocyte genes most highly expressed in mouse HSC-enriched bone marrow cells is that encoding von Willebrand factor (vWF) (7,10), a protein involved in platelet aggregation (11) and [...]

Published
2013

39. Ezh2 is essential for the generation of functional yolk sac derived erythro-myeloid progenitors

Author

Neo, W, Meng, Y, Rodriguez-Meira, A, Fadlullah, M, Booth, C, Azzoni, E, Thongjuea, S, de Bruijn, M, Jacobsen, S, Mead, A, Lacaud, G, Neo, Wen Hao, Meng, Yiran, Rodriguez-Meira, Alba, Fadlullah, Muhammad Z H, Booth, Christopher A G, Azzoni, Emanuele, Thongjuea, Supat, de Bruijn, Marella F T R, Jacobsen, Sten Eirik W, Mead, Adam J, Lacaud, Georges, Neo, W, Meng, Y, Rodriguez-Meira, A, Fadlullah, M, Booth, C, Azzoni, E, Thongjuea, S, de Bruijn, M, Jacobsen, S, Mead, A, Lacaud, G, Neo, Wen Hao, Meng, Yiran, Rodriguez-Meira, Alba, Fadlullah, Muhammad Z H, Booth, Christopher A G, Azzoni, Emanuele, Thongjuea, Supat, de Bruijn, Marella F T R, Jacobsen, Sten Eirik W, Mead, Adam J, and Lacaud, Georges

Abstract

Yolk sac (YS) hematopoiesis is critical for the survival of the embryo and a major source of tissue-resident macrophages that persist into adulthood. Yet, the transcriptional and epigenetic regulation of YS hematopoiesis remains poorly characterized. Here we report that the epigenetic regulator Ezh2 is essential for YS hematopoiesis but dispensable for subsequent aorta–gonad–mesonephros (AGM) blood development. Loss of EZH2 activity in hemogenic endothelium (HE) leads to the generation of phenotypically intact but functionally deficient erythro-myeloid progenitors (EMPs), while the generation of primitive erythroid cells is not affected. EZH2 activity is critical for the generation of functional EMPs at the onset of the endothelial-to-hematopoietic transition but subsequently dispensable. We identify a lack of Wnt signaling downregulation as the primary reason for the production of non-functional EMPs. Together, our findings demonstrate a critical and stage-specific role of Ezh2 in modulating Wnt signaling during the generation of EMPs from YS HE.

Published
2021

40. Developmental stage- and site-specific transitions in lineage specification and gene regulatory networks in human hematopoietic stem and progenitor cells

Author

Roy, Anindita, primary, Wang, Guanlin, additional, Iskander, Deena, additional, O’Byrne, Sorcha, additional, Elliott, Natalina, additional, O’Sullivan, Jennifer, additional, Buck, Gemma, additional, Heuston, Elisabeth F., additional, Wen, Wei Xiong, additional, Meira, Alba Rodriguez, additional, Hua, Peng, additional, Karadimitiris, Anastasios, additional, Mead, Adam J, additional, Bodine, David, additional, Roberts, Irene, additional, Psaila, Bethan, additional, and Thongjuea, Supat, additional

Published
2021
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41. Functional annotation of human long noncoding RNAs via molecular phenotyping

Author

Ramilowski, Jordan A., Yip, Chi Wai, Agrawal, Saumya, Chang, Jen-Chien, Ciani, Yari, Kulakovskiy, Ivan V., Mendez, Mickaël, Ooi, Jasmine Li Ching, Ouyang, John F., Parkinson, Nicholas J., Petri, Andreas, Roos, Leonie, Severin, Jessica, Yasuzawa, Kayoko, Abugessaisa, Imad, Akalin, Altuna, Antonov, Ivan V., Arner, Erik, Bonetti, Alessandro, Bono, Hidemasa, Borsari, Beatrice, Brombacher, Frank, Cameron, Christopher J.F., Cannistraci, Carlo V., Cardenas, Ryan, Cardon, Melissa, Chang, Howard, Dostie, Josée, Ducoli, Luca, Favorov, Alexander V., Fort, Alexandre, Garrido, Diego, Gil, Noa, Gimenez, Juliette, Guler, Reto, Handoko, Lusy, Harshbarger, Jayson, Hasegawa, Akira, Hasegawa, Yuki, Hashimoto, Kosuke, Hayatsu, Norihito, Heutink, Peter, Hirose, Tetsuro, Imada, Eddie L., Itoh, Masayoshi, Kaczkowski, Bogumil, Kanhere, Aditi S., Kawabata, Emily, Kawaji, Hideya, Kawashima, Tsugumi, Kelly, S. Thomas, Kojima, Miki, Kondo, Naoto, Koseki, Haruhiko, Kouno, Tsukasa, Kratz, Anton, Kurowska-Stolarska, Mariola S., Kwon, Andrew Tae Jun, Leek, Jeffrey T., Lennartsson, Andreas, Lizio, Marina, López-Redondo, Fernando, Luginbühl, Joachim, Maeda, Shiori, Makeev, Vsevolod, Marchionni, Luigi, Medvedeva, Yulia A., Minoda, Aki, Müller, Ferenc, Muñoz-Aguirre, Manuel, Murata, Mitsuyoshi, Nishiyori, Hiromi, Nitta, Kazuhiro R., Noguchi, Shuhei, Noro, Yukihiko, Nurtdinov, Ramil N., Okazaki, Yasushi, Orlando, Valerio, Paquette, Denis, Parr, Callum J.C., Rackham, Owen J.L., Rizzu, Patrizia, Sánchez Martinez, Diego Fernando, Sandelin, Albin, Sanjana, Pillay, Semple, Colin A.M., Shibayama, Youtaro, Sivaraman, Divya M., Szumowski, Suzannah C., Tagami, Michihira, Taylor, Martin S., Terao, Chikashi, Thodberg, Malte, Thongjuea, Supat, Tripathi, Vidisha, Ulitsky, Igor, Verardo, Roberto, Vorontsov, Ilya E., Yamamoto, Chinatsu, Baillie, J. Kenneth, Forrest, Alistair R.R., Guigó, Roderic, Hoffman, Michael, Hon, Chungchau, Kasukawa, Takeya, Kauppinen, Sakari, Kere, Jura, Lenhard, Boris, Schneider, Claudio, Suzuki, Harukazu, Yagi, Ken, de Hoon, Michiel J.L., Shin, Jay W., and Carninci, Piero

Abstract

Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-to-date lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2., Genome Research, 30 (7), ISSN:1088-9051, ISSN:1549-5469

Published
2020

42. Single-cell analyses reveal aberrant pathways for megakaryocyte-biased hematopoiesis in myelofibrosis and identify mutant clone-specific targets

Author

Psaila, Bethan, Wang, Guanlin, Rodriguez Meira, Alba, Li, Rong, Heuston, Elisabeth F., Murphy, Lauren, Yee, Daniel, Hitchcock, Ian Stuart, Sousos, Nikolaos, O'Sullivan, Jennifer, Anderson, Stacie, Senis, Yotis A., Weinberg, Olga K., Calicchio, Monica L., Iskander, Deena, Royston, Daniel, Milojkovic, Dragana, Roberts, Irene, Bodine, David M., Thongjuea, Supat, and Mead, Adam J.

Published
2020

43. The quiescent fraction of chronic myeloid leukemic stem cells depends on BMPR1B, Stat3 and BMP4-niche signals to persist in patients in remission

Author

Jeanpierre, Sandrine, Arizkane, Kawtar, Thongjuea, Supat, Grockowiak, Elodie, Geistlich, Kevin, Barral, Lea, Voeltzel, Thibault, Guillemin, Anissa, Gonin-Giraud, Sandrine, Gandrillon, Olivier, Nicolini, Franck-Emmanuel, Mead, Adam, Maguer-Satta, Veronique, Lefort, Sylvain, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure - Lyon (ENS Lyon), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), maguer-satta, veronique, and École normale supérieure de Lyon (ENS de Lyon)

Subjects
STAT3 Transcription Factor, education, Fusion Proteins, bcr-abl, [SDV.CAN]Life Sciences [q-bio]/Cancer, Bone Morphogenetic Protein 4, Hematopoietic Stem Cells, Article, [SDV.CAN] Life Sciences [q-bio]/Cancer, hemic and lymphatic diseases, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Neoplastic Stem Cells, Tumor Microenvironment, Humans, Protein Kinase Inhibitors, Bone Morphogenetic Protein Receptors, Type I
Abstract

Chronic myelogenous leukemia arises from the transformation of hematopoietic stem cells by the BCR-ABL oncogene. Though transformed cells are predominantly BCR-ABL-dependent and sensitive to tyrosine kinase inhibitor treatment, some BMPR1B+ leukemic stem cells are treatment-insensitive and rely, among others, on the bone morphogenetic protein (BMP) pathway for their survival via a BMP4 autocrine loop. Here, we further studied the involvement of BMP signaling in favoring residual leukemic stem cell persistence in the bone marrow of patients having achieved remission under treatment. We demonstrate by single-cell RNA-Seq analysis that a sub-fraction of surviving BMPR1B+ leukemic stem cells are co-enriched in BMP signaling, quiescence and stem cell signatures, without modulation of the canonical BMP target genes, but enrichment in actors of the Jak2/Stat3 signaling pathway. Indeed, based on a new model of persisting CD34+CD38- leukemic stem cells, we show that BMPR1B+ cells display co-activated Smad1/5/8 and Stat3 pathways. Interestingly, we reveal that only the BMPR1B+ cells adhering to stromal cells display a quiescent status. Surprisingly, this quiescence is induced by treatment, while non-adherent BMPR1B+ cells treated with tyrosine kinase inhibitors continued to proliferate. The subsequent targeting of BMPR1B and Jak2 pathways decreased quiescent leukemic stem cells by promoting their cell cycle re-entry and differentiation. Moreover, while Jak2-inhibitors alone increased BMP4 production by mesenchymal cells, the addition of the newly described BMPR1B inhibitor (E6201) impaired BMP4-mediated production by stromal cells. Altogether, our data demonstrate that targeting both BMPR1B and Jak2/Stat3 efficiently impacts persisting and dormant leukemic stem cells hidden in their bone marrow microenvironment.

Published
2020

45. Heterogeneous disease-propagating stem cells in juvenile myelomonocytic leukemia

Author

Louka, Eleni, primary, Povinelli, Benjamin, additional, Rodriguez-Meira, Alba, additional, Buck, Gemma, additional, Wen, Wei Xiong, additional, Wang, Guanlin, additional, Sousos, Nikolaos, additional, Ashley, Neil, additional, Hamblin, Angela, additional, Booth, Christopher A.G., additional, Roy, Anindita, additional, Elliott, Natalina, additional, Iskander, Deena, additional, de la Fuente, Josu, additional, Fordham, Nicholas, additional, O’Byrne, Sorcha, additional, Inglott, Sarah, additional, Norfo, Ruggiero, additional, Salio, Mariolina, additional, Thongjuea, Supat, additional, Rao, Anupama, additional, Roberts, Irene, additional, and Mead, Adam J., additional

Published
2021
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46. Single-Cell Transcriptional Landscapes of Human Bone Marrow Reveal Distinct Erythroid Phenotypes Underpinned By Genotype in Diamond-Blackfan Anemia

Author

Iskander, Deena, primary, Wang, Guanlin, additional, Heuston, Elisabeth F, additional, Christodoulidou, Chrysi, additional, Psaila, Bethan, additional, Robinson, Mark E, additional, Chaidos, Aristeidis, additional, Trivedi, Pritesh, additional, Trasanidis, Nikolaos, additional, Katsarou, Alexia, additional, Szydlo, Richard, additional, SequencingProgram, NISC Comparative, additional, Al-Oqaily, Qais, additional, Caputo, Valentina S, additional, Ponnusamy, Kanagaraju, additional, Roy, Anindita, additional, Karnik, Leena, additional, Naresh, Kikkeri, additional, Mead, Adam J., additional, Thongjuea, Supat, additional, Brand, Marjorie, additional, de la Fuente, Josu, additional, Bodine, David M., additional, Roberts, Irene, additional, and Karadimitris, Anastasios, additional

Published
2020
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50. Corrigendum: Functional annotation of human long noncoding RNAs via molecular phenotyping

Author

Ramilowski, Jordan A., primary, Yip, Chi Wai, additional, Agrawal, Saumya, additional, Chang, Jen-Chien, additional, Ciani, Yari, additional, Kulakovskiy, Ivan V., additional, Mendez, Mickaël, additional, Ooi, Jasmine Li Ching, additional, Ouyang, John F., additional, Parkinson, Nick, additional, Petri, Andreas, additional, Roos, Leonie, additional, Severin, Jessica, additional, Yasuzawa, Kayoko, additional, Abugessaisa, Imad, additional, Akalin, Altuna, additional, Antonov, Ivan V., additional, Arner, Erik, additional, Bonetti, Alessandro, additional, Bono, Hidemasa, additional, Borsari, Beatrice, additional, Brombacher, Frank, additional, Cameron, Christopher J.F., additional, Cannistraci, Carlo Vittorio, additional, Cardenas, Ryan, additional, Cardon, Melissa, additional, Chang, Howard, additional, Dostie, Josée, additional, Ducoli, Luca, additional, Favorov, Alexander, additional, Fort, Alexandre, additional, Garrido, Diego, additional, Gil, Noa, additional, Gimenez, Juliette, additional, Guler, Reto, additional, Handoko, Lusy, additional, Harshbarger, Jayson, additional, Hasegawa, Akira, additional, Hasegawa, Yuki, additional, Hashimoto, Kosuke, additional, Hayatsu, Norihito, additional, Heutink, Peter, additional, Hirose, Tetsuro, additional, Imada, Eddie L., additional, Itoh, Masayoshi, additional, Kaczkowski, Bogumil, additional, Kanhere, Aditi, additional, Kawabata, Emily, additional, Kawaji, Hideya, additional, Kawashima, Tsugumi, additional, Kelly, S. Thomas, additional, Kojima, Miki, additional, Kondo, Naoto, additional, Koseki, Haruhiko, additional, Kouno, Tsukasa, additional, Kratz, Anton, additional, Kurowska-Stolarska, Mariola, additional, Kwon, Andrew Tae Jun, additional, Leek, Jeffrey, additional, Lennartsson, Andreas, additional, Lizio, Marina, additional, López-Redondo, Fernando, additional, Luginbühl, Joachim, additional, Maeda, Shiori, additional, Makeev, Vsevolod J., additional, Marchionni, Luigi, additional, Medvedeva, Yulia A., additional, Minoda, Aki, additional, Müller, Ferenc, additional, Muñoz-Aguirre, Manuel, additional, Murata, Mitsuyoshi, additional, Nishiyori, Hiromi, additional, Nitta, Kazuhiro R., additional, Noguchi, Shuhei, additional, Noro, Yukihiko, additional, Nurtdinov, Ramil, additional, Okazaki, Yasushi, additional, Orlando, Valerio, additional, Paquette, Denis, additional, Parr, Callum J.C., additional, Rackham, Owen J.L., additional, Rizzu, Patrizia, additional, Martinez, Diego Fernando Sánchez, additional, Sandelin, Albin, additional, Sanjana, Pillay, additional, Semple, Colin A.M., additional, Shibayama, Youtaro, additional, Sivaraman, Divya M., additional, Suzuki, Takahiro, additional, Szumowski, Suzannah C., additional, Tagami, Michihira, additional, Taylor, Martin S., additional, Terao, Chikashi, additional, Thodberg, Malte, additional, Thongjuea, Supat, additional, Tripathi, Vidisha, additional, Ulitsky, Igor, additional, Verardo, Roberto, additional, Vorontsov, Ilya E., additional, Yamamoto, Chinatsu, additional, Young, Robert S., additional, Baillie, J. Kenneth, additional, Forrest, Alistair R.R., additional, Guigó, Roderic, additional, Hoffman, Michael M., additional, Hon, Chung Chau, additional, Kasukawa, Takeya, additional, Kauppinen, Sakari, additional, Kere, Juha, additional, Lenhard, Boris, additional, Schneider, Claudio, additional, Suzuki, Harukazu, additional, Yagi, Ken, additional, de Hoon, Michiel J.L., additional, Shin, Jay W., additional, and Carninci, Piero, additional

Published
2020
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