Cooperative Transcription Factor Induction Mediates Hemogenic Reprogramming

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Cooperative Transcription Factor Induction Mediates Hemogenic Reprogramming. / Gomes, Andreia M.; Kurochkin, Ilia; Chang, Betty; Daniel, Michael; Law, Kenneth; Satija, Namita; Lachmann, Alexander; Wang, Zichen; Ferreira, Lino; Ma'ayan, Avi; Chen, Benjamin K.; Papatsenko, Dmitri; Lemischka, Ihor R.; Moore, Kateri A.; Pereira, Carlos Filipe.

I: Cell Reports, 2018.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Gomes, AM, Kurochkin, I, Chang, B, Daniel, M, Law, K, Satija, N, Lachmann, A, Wang, Z, Ferreira, L, Ma'ayan, A, Chen, BK, Papatsenko, D, Lemischka, IR, Moore, KA & Pereira, CF 2018, 'Cooperative Transcription Factor Induction Mediates Hemogenic Reprogramming', Cell Reports. https://doi.org/10.1016/j.celrep.2018.11.032

APA

CBE

Gomes AM, Kurochkin I, Chang B, Daniel M, Law K, Satija N, Lachmann A, Wang Z, Ferreira L, Ma'ayan A, Chen BK, Papatsenko D, Lemischka IR, Moore KA, Pereira CF. 2018. Cooperative Transcription Factor Induction Mediates Hemogenic Reprogramming. Cell Reports. https://doi.org/10.1016/j.celrep.2018.11.032

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Author

Gomes, Andreia M. ; Kurochkin, Ilia ; Chang, Betty ; Daniel, Michael ; Law, Kenneth ; Satija, Namita ; Lachmann, Alexander ; Wang, Zichen ; Ferreira, Lino ; Ma'ayan, Avi ; Chen, Benjamin K. ; Papatsenko, Dmitri ; Lemischka, Ihor R. ; Moore, Kateri A. ; Pereira, Carlos Filipe. / Cooperative Transcription Factor Induction Mediates Hemogenic Reprogramming. I: Cell Reports. 2018.

RIS

TY - JOUR

T1 - Cooperative Transcription Factor Induction Mediates Hemogenic Reprogramming

AU - Gomes, Andreia M.

AU - Kurochkin, Ilia

AU - Chang, Betty

AU - Daniel, Michael

AU - Law, Kenneth

AU - Satija, Namita

AU - Lachmann, Alexander

AU - Wang, Zichen

AU - Ferreira, Lino

AU - Ma'ayan, Avi

AU - Chen, Benjamin K.

AU - Papatsenko, Dmitri

AU - Lemischka, Ihor R.

AU - Moore, Kateri A.

AU - Pereira, Carlos Filipe

PY - 2018

Y1 - 2018

N2 - During development, hematopoietic stem and progenitor cells (HSPCs) arise from specialized endothelial cells by a process termed endothelial-to-hematopoietic transition (EHT). The genetic program driving human HSPC emergence remains largely unknown. We previously reported that the generation of hemogenic precursor cells from mouse fibroblasts recapitulates developmental hematopoiesis. Here, we demonstrate that human fibroblasts can be reprogrammed into hemogenic cells by the same transcription factors. Induced cells display dynamic EHT transcriptional programs, generate hematopoietic progeny, possess HSPC cell surface phenotype, and repopulate immunodeficient mice for 3 months. Mechanistically, GATA2 and GFI1B interact and co-occupy a cohort of targets. This cooperative binding is reflected by engagement of open enhancers and promoters, initiating silencing of fibroblast genes and activating the hemogenic program. However, GATA2 displays dominant and independent targeting activity during the early phases of reprogramming. These findings shed light on the processes controlling human HSC specification and support generation of reprogrammed HSCs for clinical applications. Gomes et al. show that specification of hemogenesis in human fibroblasts is mediated by cooperative transcription factor binding. GATA2 displays dominance, interacts with GFI1B, and recruits FOS to open chromatin, simultaneously silencing the fibroblast program and initiating an endothelial-to-hematopoietic transition to definitive hematopoiesis.

AB - During development, hematopoietic stem and progenitor cells (HSPCs) arise from specialized endothelial cells by a process termed endothelial-to-hematopoietic transition (EHT). The genetic program driving human HSPC emergence remains largely unknown. We previously reported that the generation of hemogenic precursor cells from mouse fibroblasts recapitulates developmental hematopoiesis. Here, we demonstrate that human fibroblasts can be reprogrammed into hemogenic cells by the same transcription factors. Induced cells display dynamic EHT transcriptional programs, generate hematopoietic progeny, possess HSPC cell surface phenotype, and repopulate immunodeficient mice for 3 months. Mechanistically, GATA2 and GFI1B interact and co-occupy a cohort of targets. This cooperative binding is reflected by engagement of open enhancers and promoters, initiating silencing of fibroblast genes and activating the hemogenic program. However, GATA2 displays dominant and independent targeting activity during the early phases of reprogramming. These findings shed light on the processes controlling human HSC specification and support generation of reprogrammed HSCs for clinical applications. Gomes et al. show that specification of hemogenesis in human fibroblasts is mediated by cooperative transcription factor binding. GATA2 displays dominance, interacts with GFI1B, and recruits FOS to open chromatin, simultaneously silencing the fibroblast program and initiating an endothelial-to-hematopoietic transition to definitive hematopoiesis.

KW - cooperative binding

KW - direct cell reprogramming

KW - FOS

KW - GATA2

KW - GFI1B

KW - hematopoietic stem cell

KW - hematopoietic transcription factor

KW - hemogenic endothelium

KW - hemogenic reprogramming

KW - human endothelial-to-hematopoietic transition

U2 - 10.1016/j.celrep.2018.11.032

DO - 10.1016/j.celrep.2018.11.032

M3 - Article

JO - Cell Reports

T2 - Cell Reports

JF - Cell Reports

SN - 2211-1247

ER -