FOG-1 and GATA-1 act sequentially to specify definitive megakaryocytic and erythroid progenitors

被引：79

作者：

Mancini, Elena ^{[2
]}

Sanjuan-Pla, Alejandra ^{[1
]}

Luciani, Luisa ^{[2
]}

Moore, Susan ^{[1
]}

Grover, Amit ^{[1
]}

Zay, Agnes ^{[1
]}

Rasmussen, Kasper D. ^{[2
]}

Luc, Sidinh ^{[3
]}

Bilbao, Daniel ^{[2
]}

O'Carroll, Donal ^{[2
]}

Jacobsen, Sten Eirik ^{[3
]}

Nerlov, Claus ^{[1
,2
]}

机构：

[1] Univ Edinburgh, MRC Ctr Regenerat Med, Inst Stem Cell Res, Edinburgh EH9 3JQ, Midlothian, Scotland

[2] EMBL Mouse Biol Unit, Monterotondo, Italy

[3] Univ Oxford, Weatherall Inst Mol Med, Haemopoiet Stem Cell Lab, Oxford, England

来源：

EMBO JOURNAL | 2012年 / 31卷 / 02期

基金：

英国医学研究理事会; 瑞典研究理事会;

关键词：

haematopoiesis; lineage commitment; stem cells; transcription; MULTIPOTENT HEMATOPOIETIC PROGENITORS; TRANSCRIPTION FACTOR GATA-1; MYELOID LINEAGE COMMITMENT; LEUKEMIA-INITIATING CELLS; C/EBP-ALPHA BINDS; GENE-EXPRESSION; STEM-CELLS; MICE LACKING; ADIPOCYTE DIFFERENTIATION; PROLIFERATION ARREST;

D O I：

10.1038/emboj.2011.390

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The transcription factors that control lineage specification of haematopoietic stem cells (HSCs) have been well described for the myeloid and lymphoid lineages, whereas transcriptional control of erythroid (E) and megakaryocytic (Mk) fate is less understood. We here use conditional removal of the GATA-1 and FOG-1 transcription factors to identify FOG-1 as required for the formation of all committed Mk- and E-lineage progenitors, whereas GATA-1 was observed to be specifically required for E-lineage commitment. FOG-1-deficient HSCs and preMegEs, the latter normally bipotent for the Mk and E lineages, underwent myeloid transcriptional reprogramming, and formed myeloid, but not erythroid and megakaryocytic cells in vitro. These results identify FOG-1 and GATA-1 as required for formation of bipotent Mk/E progenitors and their E-lineage commitment, respectively, and show that FOG-1 mediates transcriptional Mk/E programming of HSCs as well as their subsequent Mk/E-lineage commitment. Finally, C/EBPs and FOG-1 exhibited transcriptional cross-regulation in early myelo-erythroid progenitors making their functional antagonism a potential mechanism for separation of the myeloid and Mk/E lineages. The EMBO Journal (2012) 31, 351-365. doi:10.1038/emboj.2011.390; Published online 8 November 2011

引用

页码：351 / 365

页数：15

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