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 & 46 others 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

    Research output: Contribution to journalArticle

    119 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 languageEnglish
    Article number1251033
    Pages (from-to)1-10
    JournalScience
    Volume345
    Issue number6204
    DOIs
    Publication statusPublished - 26 Sep 2014

    Fingerprint

    NFI Transcription Factors
    Regenerative Medicine
    Megakaryocytes
    Alternative Splicing
    Hematopoietic Stem Cells
    Population
    Genes
    Blood Cells
    Protein Isoforms
    Blood Platelets
    Transplantation
    RNA
    Gene Expression

    Cite this

    Chen, L., Kostadima, M., Martens, J., Canu, G., Garcia, S., Turro, E., ... Rendon, A. (2014). Transcriptional diversity during lineage commitment of human blood progenitors. Science, 345(6204), 1-10. [1251033]. https://doi.org/10.1126/science.1251033
    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 ; Chambers, J C ; Choudry, F A ; Clarke, L ; Coupland, P ; Van Der Ent, M ; Erber, Wendy ; Jansen, J H ; Favier, R ; Fenech, M E ; Foad, N ; Freson, K ; Van Geet, C ; Gomez, K ; Guigo, R ; Hampshire, D ; Kelly, A M ; Kerstens, H H D ; Kooner, J S ; Laffan, M ; Lentaigne, C ; Labalette, C ; Martin, T ; Meacham, S ; Mumford, A ; Nurnberg, S ; Palumbo, E ; Van Der Reijden, B A ; Richardson, D ; Sammut, S J ; Slodkowicz, G ; Tamuri, A U ; 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, W H ; Stunnenberg, H G ; Frontini, M ; Rendon, A. / Transcriptional diversity during lineage commitment of human blood progenitors. In: Science. 2014 ; Vol. 345, No. 6204. pp. 1-10.
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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.",
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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

    Transcriptional diversity during lineage commitment of human blood progenitors. / 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; Chambers, J C; Choudry, F A; Clarke, L; Coupland, P; Van Der Ent, M; Erber, Wendy; Jansen, J H; Favier, R; Fenech, M E; Foad, N; Freson, K; Van Geet, C; Gomez, K; Guigo, R; Hampshire, D; Kelly, A M; Kerstens, H H D; Kooner, J S; Laffan, M; Lentaigne, C; Labalette, C; Martin, T; Meacham, S; Mumford, A; Nurnberg, S; Palumbo, E; Van Der Reijden, B A; Richardson, D; Sammut, S J; Slodkowicz, G; Tamuri, A U; 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, W H; Stunnenberg, H G; Frontini, M; Rendon, A.

    In: Science, Vol. 345, No. 6204, 1251033, 26.09.2014, p. 1-10.

    Research output: Contribution to journalArticle

    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.

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    DO - 10.1126/science.1251033

    M3 - Article

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    EP - 10

    JO - Science

    JF - Science

    SN - 0036-8075

    IS - 6204

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    Chen L, Kostadima M, Martens J, Canu G, Garcia S, Turro E et al. Transcriptional diversity during lineage commitment of human blood progenitors. Science. 2014 Sep 26;345(6204):1-10. 1251033. https://doi.org/10.1126/science.1251033