The T-box transcription factor Eomesodermin governs haemogenic competence of yolk sac mesodermal progenitors.
The T-box transcription factor Eomesodermin governs haemogenic competence of yolk sac mesodermal progenitors.
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T-box转录因子Eomesodermin控制蛋黄中胚层祖细胞的血液原性。
DOI：
10.1038/s41556-020-00611-8
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发表时间：
2021-01
影响因子：
21.3
通讯作者：
Robertson EJ
中科院分区：
文献类型：
--
作者：
Harland LTG;Simon CS;Senft AD;Costello I;Greder L;Imaz-Rosshandler I;Göttgens B;Marioni JC;Bikoff EK;Porcher C;de Bruijn MFTR;Robertson EJ
胚外中胚层（ExM）是穿过原条（PS）的最早细胞，在发育中的卵黄囊（YS）中产生内皮细胞和造血祖细胞。ExM的特定子集如何致力于造血命运仍不清楚。在这里，我们证明了使用胚胎干细胞（ESC）模型，瞬时表达的T-盒转录因子Eomesodermin（Eomes）支配造血能力的ExM。Eomes调节SCL通常用于指定原始红细胞的增强子的可及性，并且对于Runx 1+造血内皮的正常发育至关重要。单细胞RNA-seq表明，Eomes功能丧失严重阻断血液祖细胞的形成，但不特异化Flk-1+血内皮祖细胞。我们的研究结果将Eomes置于调节早期血液形成的转录层次的顶部，并表明在胚胎发育过程中，生血能力比以前认识到的更早。
Extra-embryonic mesoderm (ExM), the earliest cells that traverse the primitive streak (PS), give rise to the endothelium as well as hematopoietic progenitors in the developing yolk-sac (YS). How a specific subset of ExM becomes committed to a hematopoietic fate remains unclear. Here we demonstrate using an embryonic stem cell (ESC) model that transient expression of the T-box transcription factor Eomesodermin (Eomes) governs hemogenic competency of ExM. Eomes regulates the accessibility of enhancers that SCL normally utilizes to specify primitive erythrocytes and is essential for the normal development of Runx1+ hemogenic endothelium. Single-cell-RNA-seq suggests that Eomes loss-of-function profoundly blocks formation of blood progenitors but not specification of Flk-1+ hematoendothelial progenitors. Our findings place Eomes at the top of the transcriptional hierarchy regulating early blood formation and suggest that hemogenic competence is endowed earlier during embryonic development than previously appreciated.
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影响因子：
11.8
作者：
Goode DK;Obier N;Vijayabaskar MS;Lie-A-Ling M;Lilly AJ;Hannah R;Lichtinger M;Batta K;Florkowska M;Patel R;Challinor M;Wallace K;Gilmour J;Assi SA;Cauchy P;Hoogenkamp M;Westhead DR;Lacaud G;Kouskoff V;Göttgens B;Bonifer C
通讯作者：
Bonifer C
影响因子：
4.6
作者：
Fitch, Simon R.;Kapeni, Chrysa;Ottersbach, Katrin
通讯作者：
Ottersbach, Katrin
影响因子：
2.6
作者：
Ferkowicz, MJ;Yoder, MC
通讯作者：
Yoder, MC
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK
DOI：
10.1242/dev.014357
发表时间：
2008-02
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Arnold SJ;Hofmann UK;Bikoff EK;Robertson EJ
通讯作者：
Robertson EJ