Transcriptional diversity during lineage commitment of human blood progenitors

L Chen; M Kostadima; J Martens; G Canu; S Garcia; E Turro; K Downes; I Macaulay; E Bielczyk-Maczynska; S Coe; S Farrow; P Poudel; F Burden; S B G Jansen; W Astle; A Attwood; T Bariana; B De Bono; A Breschi; J C Chambers; F A Choudry; L Clarke; P Coupland; M Van Der Ent; Wendy Erber; J H Jansen; R Favier; M E Fenech; N Foad; K Freson; C Van Geet; K Gomez; R Guigo; D Hampshire; A M Kelly; H H D Kerstens; J S Kooner; M Laffan; C Lentaigne; C Labalette; T Martin; S Meacham; A Mumford; S Nurnberg; E Palumbo; B A Van Der Reijden; D Richardson; S J Sammut; G Slodkowicz; A U Tamuri; L Vasquez; K Voss; S Watt; S Westbury; P Flicek; R Loos; N Goldman; P Bertone; RJ Read; S Richardson; A Cvejic; N Soranzo; W H Ouwehand; H G Stunnenberg; M Frontini; A Rendon

doi:10.1126/science.1251033

Transcriptional diversity during lineage commitment of human blood progenitors

L Chen, M Kostadima, J Martens, G Canu, S Garcia, E Turro, K Downes, I Macaulay, E Bielczyk-Maczynska, S Coe, S Farrow, P Poudel, F Burden, S B G Jansen, W Astle, A Attwood, T Bariana, B De Bono, A Breschi, J C ChambersF A Choudry, L Clarke, P Coupland, M Van Der Ent, Wendy Erber, J H Jansen, R Favier, M E Fenech, N Foad, K Freson, C Van Geet, K Gomez, R Guigo, D Hampshire, A M Kelly, H H D Kerstens, J S Kooner, M Laffan, C Lentaigne, C Labalette, T Martin, S Meacham, A Mumford, S Nurnberg, E Palumbo, B A Van Der Reijden, D Richardson, S J Sammut, G Slodkowicz, A U Tamuri, L Vasquez, K Voss, S Watt, S Westbury, P Flicek, R Loos, N Goldman, P Bertone, RJ Read, S Richardson, A Cvejic, N Soranzo, W H Ouwehand, H G Stunnenberg, M Frontini, A Rendon

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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
Article number	1251033
Pages (from-to)	1-10
Journal	Science
Volume	345
Issue number	6204
DOIs	https://doi.org/10.1126/science.1251033
Publication status	Published - 26 Sept 2014

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10.1126/science.1251033

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4254742/

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Chen, L., Kostadima, M., Martens, J., Canu, G., Garcia, S., Turro, E., Downes, K., Macaulay, I., Bielczyk-Maczynska, E., Coe, S., Farrow, S., Poudel, P., Burden, F., Jansen, S. B. G., Astle, W., Attwood, A., Bariana, T., De Bono, B., Breschi, A., ... Rendon, A. (2014). Transcriptional diversity during lineage commitment of human blood progenitors. Science, 345(6204), 1-10. Article 1251033. https://doi.org/10.1126/science.1251033

@article{8c02d43cf53a4857964d4b9833a840b2,

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 = "L Chen and M Kostadima and J Martens and G Canu and S Garcia and E Turro and K Downes and I Macaulay and E Bielczyk-Maczynska and S Coe and S Farrow and P Poudel and F Burden and Jansen, {S B G} and W Astle and A Attwood and T Bariana and {De Bono}, B and A Breschi and Chambers, {J C} and Choudry, {F A} and L Clarke and P Coupland and {Van Der Ent}, M and Wendy Erber and Jansen, {J H} and R Favier and Fenech, {M E} and N Foad and K Freson and {Van Geet}, C and K Gomez and R Guigo and D Hampshire and Kelly, {A M} and Kerstens, {H H D} and Kooner, {J S} and M Laffan and C Lentaigne and C Labalette and T Martin and S Meacham and A Mumford and S Nurnberg and E Palumbo and {Van Der Reijden}, {B A} and D Richardson and Sammut, {S J} and G Slodkowicz and Tamuri, {A U} and L Vasquez and K Voss and S Watt and S Westbury and P Flicek and R Loos and N Goldman and P Bertone and RJ Read and S Richardson and A Cvejic and N Soranzo and Ouwehand, {W H} and Stunnenberg, {H G} and M Frontini and A Rendon",

year = "2014",

month = sep,

day = "26",

doi = "10.1126/science.1251033",

language = "English",

volume = "345",

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Chen, L, Kostadima, M, Martens, J, Canu, G, Garcia, S, Turro, E, Downes, K, Macaulay, I, Bielczyk-Maczynska, E, Coe, S, Farrow, S, Poudel, P, Burden, F, Jansen, SBG, Astle, W, Attwood, A, Bariana, T, De Bono, B, Breschi, A, Chambers, JC, Choudry, FA, Clarke, L, Coupland, P, Van Der Ent, M, Erber, W, 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, Nurnberg, S, 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, Stunnenberg, HG, Frontini, M & Rendon, A 2014, 'Transcriptional diversity during lineage commitment of human blood progenitors', Science, vol. 345, no. 6204, 1251033, pp. 1-10. https://doi.org/10.1126/science.1251033

TY - JOUR

T1 - Transcriptional diversity during lineage commitment of human blood progenitors

AU - Chen, L

AU - Kostadima, M

AU - Martens, J

AU - Canu, G

AU - Garcia, S

AU - Turro, E

AU - Downes, K

AU - Macaulay, I

AU - Bielczyk-Maczynska, E

AU - Coe, S

AU - Farrow, S

AU - Poudel, P

AU - Burden, F

AU - Jansen, S B G

AU - Astle, W

AU - Attwood, A

AU - Bariana, T

AU - De Bono, B

AU - Breschi, A

AU - Chambers, J C

AU - Choudry, F A

AU - Clarke, L

AU - Coupland, P

AU - Van Der Ent, M

AU - Erber, Wendy

AU - Jansen, J H

AU - Favier, R

AU - Fenech, M E

AU - Foad, N

AU - Freson, K

AU - Van Geet, C

AU - Gomez, K

AU - Guigo, R

AU - Hampshire, D

AU - Kelly, A M

AU - Kerstens, H H D

AU - Kooner, J S

AU - Laffan, M

AU - Lentaigne, C

AU - Labalette, C

AU - Martin, T

AU - Meacham, S

AU - Mumford, A

AU - Nurnberg, S

AU - Palumbo, E

AU - Van Der Reijden, B A

AU - Richardson, D

AU - Sammut, S J

AU - Slodkowicz, G

AU - Tamuri, A U

AU - Vasquez, L

AU - Voss, K

AU - Watt, S

AU - Westbury, S

AU - Flicek, P

AU - Loos, R

AU - Goldman, N

AU - Bertone, P

AU - Read, RJ

AU - Richardson, S

AU - Cvejic, A

AU - Soranzo, N

AU - Ouwehand, W H

AU - Stunnenberg, H G

AU - Frontini, M

AU - Rendon, A

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

C2 - 25258084

SN - 0036-8075

VL - 345

SP - 1

EP - 10

JO - Science

JF - Science

IS - 6204

M1 - 1251033

ER -

Transcriptional diversity during lineage commitment of human blood progenitors

Abstract

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