Transcriptional diversity during lineage commitment of human blood progenitors

被引：210

作者：

Chen, Lu ^{[1
,2
,3
]}

Kostadima, Myrto ^{[2
,3
,4
]}

Martens, Joost H. A. ^{[5
]}

Canu, Giovanni ^{[2
,3
]}

Garcia, Sara P. ^{[2
,3
]}

Turro, Ernest ^{[2
,3
]}

Downes, Kate ^{[2
,3
]}

Macaulay, Iain C. ^{[6
]}

Bielczyk-Maczynska, Ewa ^{[2
,3
]}

Coe, Sophia ^{[2
,3
]}

Farrow, Samantha ^{[2
,3
]}

Poudel, Pawan ^{[2
,3
]}

Burden, Frances ^{[2
,3
]}

Jansen, Sjoert B. G. ^{[2
,3
]}

Astle, William J. ^{[2
,3
,7
]}

Attwood, Antony ^{[2
,3
]}

Bariana, Tadbir ^{[8
,9
,10
]}

de Bono, Bernard ^{[11
,12
]}

Breschi, Alessandra ^{[13
,14
]}

Chambers, John C. ^{[15
,16
]}

Choudry, Fizzah A. ^{[2
,3
]}

Clarke, Laura ^{[4
]}

Coupland, Paul ^{[1
]}

van der Ent, Martijn ^{[5
]}

Erber, Wendy N. ^{[17
]}

Jansen, Joop H. ^{[18
]}

Favier, Remi ^{[19
]}

Fenech, Matthew E. ^{[20
]}

Foad, Nicola ^{[2
,3
]}

Freson, Kathleen ^{[21
]}

van Geet, Chris ^{[21
]}

Gomez, Keith ^{[9
,10
]}

Guigo, Roderic ^{[13
,14
]}

Hampshire, Daniel ^{[2
,3
]}

Kelly, Anne M. ^{[2
,3
,22
]}

Kerstens, Hindrik H. D. ^{[5
]}

Kooner, Jaspal S. ^{[15
,16
]}

Laffan, Michael ^{[23
]}

Lentaigne, Claire ^{[23
]}

Labalette, Charlotte ^{[2
,3
]}

Martin, Tiphaine ^{[2
,3
,24
]}

Meacham, Stuart ^{[2
,3
]}

Mumford, Andrew ^{[25
]}

Nuernberg, Sylvia ^{[2
,3
]}

Palumbo, Emilio ^{[13
,14
]}

van der Reijden, Bert A. ^{[18
]}

Richardson, David ^{[4
]}

Sammut, Stephen J. ^{[26
,27
]}

Slodkowicz, Greg ^{[4
]}

Tamuri, Asif U. ^{[4
]}

机构：

[1] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England

[2] Univ Cambridge, Dept Haematol, Cambridge CB2 0PT, England

[3] Natl Hlth Serv NHS Blood & Transplant, Cambridge CB2 0PT, England

[4] European Bioinformat Inst, European Mol Biol Lab, Cambridge CB10 1SD, England

[5] Radboud Univ Nijmegen, Dept Mol Biol, NL-6525 GA Nijmegen, Netherlands

[6] Wellcome Trust Sanger Inst, EBI Single Cell Genom Ctr, Sanger Inst, Cambridge CB10 1SA, England

[7] MRC, Biostat Unit, Cambridge CB2 0SR, England

[8] UCL, Inst Canc, Dept Haematol, London WC1E 6DD, England

[9] Royal Free NHS Trust, Katharine Dormandy Haemophilia Ctr, London NW3 2QG, England

[10] Royal Free NHS Trust, Thrombosis Unit, London NW3 2QG, England

[11] UCL, CHIME Inst, London NW1 2DA, England

[12] Univ Auckland, Auckland Bioengn Inst, Auckland 1010, New Zealand

[13] Ctr Genom Regulat, Barcelona 08002, Spain

[14] Univ Pompeu Fabra, Barcelona 08002, Spain

[15] Imperial Coll Healthcare NHS Trust, London W12 0HS, England

[16] Ealing Hosp NHS Trust, Southall UB1 3HW, Middx, England

[17] Univ Western Australia, Crawley, WA 6009, Australia

[18] Radboud Univ Nijmegen, Med Ctr, Hematol Lab, Dept Lab Med, NL-6525 GA Nijmegen, Netherlands

[19] AP HP, INSERM U1009, F-94805 Villejuif, France

[20] Univ E Anglia, Norwich Med Sch, Biomed Res Ctr, Norwich NR4 7TJ, Norfolk, England

[21] Univ Leuven, Ctr Mol & Vasc Biol, B-3000 Leuven, Belgium

[22] Cambridge Univ Hosp NHS Fdn Trust, Cambridge B2 0QQ, England

[23] Univ London Imperial Coll Sci Technol & Med, Acad Hlth Sci Ctr, Dept Haematol, London W12 0HS, England

[24] Kings Coll London, St Thomas Hosp, Genet & Mol Med Div, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England

[25] Univ Bristol, Sch Cellular & Mol Med, Bristol BS8 1TD, Avon, England

[26] Addenbrookes Cambridge Univ Hosp NHS Trust, Dept Oncol, Cambridge CB2 0RE, England

[27] Canc Res UK, Cambridge Inst, Cambridge CB2 0RE, England

[28] Univ Bristol, Sch Clin Sci, Bristol BS2 8DZ, Avon, England

[29] European Mol Biol Lab, Genome Biol Unit, D-69117 Heidelberg, Germany

[30] European Mol Biol Lab, Dev Biol Unit, D-69117 Heidelberg, Germany

[31] Univ Cambridge, Wellcome Trust, MRC, Stem Cell Inst, Cambridge CB2 1QR, England

[32] Univ Cambridge, Cambridge Inst Med Res, Dept Haematol, Cambridge CB2 0XY, England

来源：

SCIENCE | 2014年 / 345卷 / 6204期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

HEMATOPOIETIC STEM-CELLS; NUCLEAR FACTOR-I; RNA-SEQ; GENE; DIFFERENTIATION; EXPRESSION; BINDING; GENOME; MEGAKARYOPOIESIS; MYELODYSPLASIA;

D O I：

10.1126/science.1251033

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1580 / +

页数：11

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