Transcriptional diversity during lineage commitment of human blood progenitors

Lu Chen; Myrto Kostadima; Joost H. A. Martens; Giovanni Canu; Sara P. Garcia; Ernest Turro; Kate Downes; Iain C. Macaulay; Ewa Bielczyk-Maczynska; Sophia Coe; Samantha Farrow; Pawan Poudel; Frances Burden; Sjoert B. G. Jansen; William J. Astle; Antony Attwood; Tadbir Bariana; Bernard de Bono; Alessandra Breschi; John C. Chambers; Fizzah A. Choudry; Laura Clarke; Paul Coupland; Martjin van der Ent; Wendy N. Erber; Joop H. Jansen; Rémi Favier; Matthew E. Fenech; Nicola Foad; Kathleen Freson; Chris van Geet; Keith Gomez; Roderic Guigo; Daniel Hampshire; Anne M. Kelly; Hindrik H. D. Kerstens; Jaspal S. Kooner; Michael Laffan; Claire Lentaigne; Charlotte Labalette; Tiphaine Martin; Stuart Meacham; Andrew Mumford; Sylvia T. Nürnberg; Emilio Palumbo; Bert A. van der Reijden; David Richardson; Stephen J. Sammut; Greg Slodkowicz; Asif U. Tamuri; Louella Vasquez; Katrin Voss; Stephen Watt; Sarah Westbury; Paul Flicek; Remco Loos; Nick Goldman; Paul Bertone; Randy J, Read; Sylvia Richardson; Ana Cvejic; Nicole Soranzo; Willem H. Ouwehand; Hendrik G. Stunnenburg; Mattia Frontini; Augusto Rendon

doi:10.1126/science.1251033

Transcriptional diversity during lineage commitment of human blood progenitors

Lu Chen, Myrto Kostadima, Joost H. A. Martens, Giovanni Canu, Sara P. Garcia, Ernest Turro, Kate Downes, Iain C. Macaulay, Ewa Bielczyk-Maczynska, Sophia Coe, Samantha Farrow, Pawan Poudel, Frances Burden, Sjoert B. G. Jansen, William J. Astle, Antony Attwood, Tadbir Bariana, Bernard de Bono, Alessandra Breschi, John C. ChambersFizzah A. Choudry, Laura Clarke, Paul Coupland, Martjin van der Ent, Wendy N. Erber, Joop H. Jansen, Rémi Favier, Matthew E. Fenech, Nicola Foad, Kathleen Freson, Chris van Geet, Keith Gomez, Roderic Guigo, Daniel Hampshire, Anne M. Kelly, Hindrik H. D. Kerstens, Jaspal S. Kooner, Michael Laffan, Claire Lentaigne, Charlotte Labalette, Tiphaine Martin, Stuart Meacham, Andrew Mumford, Sylvia T. Nürnberg, Emilio Palumbo, Bert A. van der Reijden, David Richardson, Stephen J. Sammut, Greg Slodkowicz, Asif U. Tamuri, Louella Vasquez, Katrin Voss, Stephen Watt, Sarah Westbury, Paul Flicek, Remco Loos, Nick Goldman, Paul Bertone, Randy J, Read, Sylvia Richardson, Ana Cvejic, Nicole Soranzo, Willem H. Ouwehand, Hendrik G. Stunnenburg, Mattia Frontini, Augusto Rendon

Norwich Medical School

Research output: Contribution to journal › Article › peer-review

215 Citations (Scopus)

Abstract

Blood cells derive from hematopoietic stem cells through stepwise fating events. To characterize gene expression programs driving lineage choice, we sequenced RNA from eight primary human hematopoietic progenitor populations representing the major myeloid commitment stages and the main lymphoid stage. We identified extensive cell type-specific expression changes: 6711 genes and 10,724 transcripts, enriched in non-protein-coding elements at early stages of differentiation. In addition, we found 7881 novel splice junctions and 2301 differentially used alternative splicing events, enriched in genes involved in regulatory processes. We demonstrated experimentally cell-specific isoform usage, identifying nuclear factor I/B (NFIB) as a regulator of megakaryocyte maturation-the platelet precursor. Our data highlight the complexity of fating events in closely related progenitor populations, the understanding of which is essential for the advancement of transplantation and regenerative medicine.

Original language	English
Journal	Science
Volume	345
Issue number	6204
DOIs	https://doi.org/10.1126/science.1251033
Publication status	Published - 26 Sep 2014

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Cite this

Chen, L., Kostadima, M., Martens, J. H. A., Canu, G., Garcia, S. P., Turro, E., Downes, K., Macaulay, I. C., Bielczyk-Maczynska, E., Coe, S., Farrow, S., Poudel, P., Burden, F., Jansen, S. B. G., Astle, W. J., Attwood, A., Bariana, T., de Bono, B., Breschi, A., ... Rendon, A. (2014). Transcriptional diversity during lineage commitment of human blood progenitors. Science, 345(6204). https://doi.org/10.1126/science.1251033

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title = "Transcriptional diversity during lineage commitment of human blood progenitors",

abstract = "Blood cells derive from hematopoietic stem cells through stepwise fating events. To characterize gene expression programs driving lineage choice, we sequenced RNA from eight primary human hematopoietic progenitor populations representing the major myeloid commitment stages and the main lymphoid stage. We identified extensive cell type-specific expression changes: 6711 genes and 10,724 transcripts, enriched in non-protein-coding elements at early stages of differentiation. In addition, we found 7881 novel splice junctions and 2301 differentially used alternative splicing events, enriched in genes involved in regulatory processes. We demonstrated experimentally cell-specific isoform usage, identifying nuclear factor I/B (NFIB) as a regulator of megakaryocyte maturation-the platelet precursor. Our data highlight the complexity of fating events in closely related progenitor populations, the understanding of which is essential for the advancement of transplantation and regenerative medicine.",

author = "Lu Chen and Myrto Kostadima and Martens, {Joost H. A.} and Giovanni Canu and Garcia, {Sara P.} and Ernest Turro and Kate Downes and Macaulay, {Iain C.} and Ewa Bielczyk-Maczynska and Sophia Coe and Samantha Farrow and Pawan Poudel and Frances Burden and Jansen, {Sjoert B. G.} and Astle, {William J.} and Antony Attwood and Tadbir Bariana and {de Bono}, Bernard and Alessandra Breschi and Chambers, {John C.} and Choudry, {Fizzah A.} and Laura Clarke and Paul Coupland and {van der Ent}, Martjin and Erber, {Wendy N.} and Jansen, {Joop H.} and R{\'e}mi Favier and Fenech, {Matthew E.} and Nicola Foad and Kathleen Freson and {van Geet}, Chris and Keith Gomez and Roderic Guigo and Daniel Hampshire and Kelly, {Anne M.} and Kerstens, {Hindrik H. D.} and Kooner, {Jaspal S.} and Michael Laffan and Claire Lentaigne and Charlotte Labalette and Tiphaine Martin and Stuart Meacham and Andrew Mumford and N{\"u}rnberg, {Sylvia T.} and Emilio Palumbo and {van der Reijden}, {Bert A.} and David Richardson and Sammut, {Stephen J.} and Greg Slodkowicz and Tamuri, {Asif U.} and Louella Vasquez and Katrin Voss and Stephen Watt and Sarah Westbury and Paul Flicek and Remco Loos and Nick Goldman and Paul Bertone and Read, {Randy J,} and Sylvia Richardson and Ana Cvejic and Nicole Soranzo and Ouwehand, {Willem H.} and Stunnenburg, {Hendrik G.} and Mattia Frontini and Augusto Rendon",

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day = "26",

doi = "10.1126/science.1251033",

language = "English",

volume = "345",

journal = "Science",

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publisher = "American Association for the Advancement of Science",

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Chen, L, Kostadima, M, Martens, JHA, Canu, G, Garcia, SP, Turro, E, Downes, K, Macaulay, IC, Bielczyk-Maczynska, E, Coe, S, Farrow, S, Poudel, P, Burden, F, Jansen, SBG, Astle, WJ, Attwood, A, Bariana, T, de Bono, B, Breschi, A, Chambers, JC, Choudry, FA, Clarke, L, Coupland, P, van der Ent, M, Erber, WN, Jansen, JH, Favier, R, Fenech, ME, Foad, N, Freson, K, van Geet, C, Gomez, K, Guigo, R, Hampshire, D, Kelly, AM, Kerstens, HHD, Kooner, JS, Laffan, M, Lentaigne, C, Labalette, C, Martin, T, Meacham, S, Mumford, A, Nürnberg, ST, Palumbo, E, van der Reijden, BA, Richardson, D, Sammut, SJ, Slodkowicz, G, Tamuri, AU, Vasquez, L, Voss, K, Watt, S, Westbury, S, Flicek, P, Loos, R, Goldman, N, Bertone, P, Read, RJ, Richardson, S, Cvejic, A, Soranzo, N, Ouwehand, WH, Stunnenburg, HG, Frontini, M & Rendon, A 2014, 'Transcriptional diversity during lineage commitment of human blood progenitors', Science, vol. 345, no. 6204. https://doi.org/10.1126/science.1251033

TY - JOUR

T1 - Transcriptional diversity during lineage commitment of human blood progenitors

AU - Chen, Lu

AU - Kostadima, Myrto

AU - Martens, Joost H. A.

AU - Canu, Giovanni

AU - Garcia, Sara P.

AU - Turro, Ernest

AU - Downes, Kate

AU - Macaulay, Iain C.

AU - Bielczyk-Maczynska, Ewa

AU - Coe, Sophia

AU - Farrow, Samantha

AU - Poudel, Pawan

AU - Burden, Frances

AU - Jansen, Sjoert B. G.

AU - Astle, William J.

AU - Attwood, Antony

AU - Bariana, Tadbir

AU - de Bono, Bernard

AU - Breschi, Alessandra

AU - Chambers, John C.

AU - Choudry, Fizzah A.

AU - Clarke, Laura

AU - Coupland, Paul

AU - van der Ent, Martjin

AU - Erber, Wendy N.

AU - Jansen, Joop H.

AU - Favier, Rémi

AU - Fenech, Matthew E.

AU - Foad, Nicola

AU - Freson, Kathleen

AU - van Geet, Chris

AU - Gomez, Keith

AU - Guigo, Roderic

AU - Hampshire, Daniel

AU - Kelly, Anne M.

AU - Kerstens, Hindrik H. D.

AU - Kooner, Jaspal S.

AU - Laffan, Michael

AU - Lentaigne, Claire

AU - Labalette, Charlotte

AU - Martin, Tiphaine

AU - Meacham, Stuart

AU - Mumford, Andrew

AU - Nürnberg, Sylvia T.

AU - Palumbo, Emilio

AU - van der Reijden, Bert A.

AU - Richardson, David

AU - Sammut, Stephen J.

AU - Slodkowicz, Greg

AU - Tamuri, Asif U.

AU - Vasquez, Louella

AU - Voss, Katrin

AU - Watt, Stephen

AU - Westbury, Sarah

AU - Flicek, Paul

AU - Loos, Remco

AU - Goldman, Nick

AU - Bertone, Paul

AU - Read, Randy J,

AU - Richardson, Sylvia

AU - Cvejic, Ana

AU - Soranzo, Nicole

AU - Ouwehand, Willem H.

AU - Stunnenburg, Hendrik G.

AU - Frontini, Mattia

AU - Rendon, Augusto

PY - 2014/9/26

Y1 - 2014/9/26

N2 - Blood cells derive from hematopoietic stem cells through stepwise fating events. To characterize gene expression programs driving lineage choice, we sequenced RNA from eight primary human hematopoietic progenitor populations representing the major myeloid commitment stages and the main lymphoid stage. We identified extensive cell type-specific expression changes: 6711 genes and 10,724 transcripts, enriched in non-protein-coding elements at early stages of differentiation. In addition, we found 7881 novel splice junctions and 2301 differentially used alternative splicing events, enriched in genes involved in regulatory processes. We demonstrated experimentally cell-specific isoform usage, identifying nuclear factor I/B (NFIB) as a regulator of megakaryocyte maturation-the platelet precursor. Our data highlight the complexity of fating events in closely related progenitor populations, the understanding of which is essential for the advancement of transplantation and regenerative medicine.

AB - Blood cells derive from hematopoietic stem cells through stepwise fating events. To characterize gene expression programs driving lineage choice, we sequenced RNA from eight primary human hematopoietic progenitor populations representing the major myeloid commitment stages and the main lymphoid stage. We identified extensive cell type-specific expression changes: 6711 genes and 10,724 transcripts, enriched in non-protein-coding elements at early stages of differentiation. In addition, we found 7881 novel splice junctions and 2301 differentially used alternative splicing events, enriched in genes involved in regulatory processes. We demonstrated experimentally cell-specific isoform usage, identifying nuclear factor I/B (NFIB) as a regulator of megakaryocyte maturation-the platelet precursor. Our data highlight the complexity of fating events in closely related progenitor populations, the understanding of which is essential for the advancement of transplantation and regenerative medicine.

U2 - 10.1126/science.1251033

DO - 10.1126/science.1251033

M3 - Article

VL - 345

JO - Science

JF - Science

SN - 0036-8075

IS - 6204

ER -