Megakaryocyte production is sustained by direct differentiation from erythromyeloid progenitors in the yolk sac until midgestation.
Megakaryocyte production is sustained by direct differentiation from erythromyeloid progenitors in the yolk sac until midgestation.
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DOI：
10.1016/j.immuni.2021.04.026
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发表时间：
2021-07-13
期刊：
影响因子：
32.4
通讯作者：
Gomez Perdiguero E
中科院分区：
文献类型：
--
作者：
Iturri L;Freyer L;Biton A;Dardenne P;Lallemand Y;Gomez Perdiguero E
胚胎外卵黄囊包含第一个确定的多能造血细胞，称为红髓祖细胞。它们起源于造血干细胞出现之前的原位，并产生红细胞、单核细胞、粒细胞、肥大细胞和巨噬细胞，后者以Myb转录因子独立的方式产生。我们在单细胞水平上发现了卵黄囊红髓系祖细胞的异质性，并在胎儿肝脏定植之前区分了多能祖细胞和固定祖细胞。我们确定了两种时间上不同的巨核细胞分化途径。第一种发生在卵黄囊，绕过中间的双能巨核细胞-红细胞祖细胞，与巨噬细胞的分化类似，是不依赖于myb的。相比之下，第二种起源于较晚的myb依赖性双能祖细胞，表达Csf2rb并定植于胎儿肝脏，在那里它们产生巨核细胞和大量红细胞。了解巨核细胞的发育是至关重要的，因为它们在血管发育过程中起着关键作用，特别是在分离血液和淋巴网络方面。在胚胎肝脏定植之前，EMP产生了局部稳定的祖细胞，在单细胞水平上发现了两波连续的EMP分化，卵黄囊Mk主要以myb不依赖的方式从EMP发育而来，CD131在卵黄囊中发现了myb依赖的EMP来源的MEP祖细胞，卵黄囊在胚胎发育过程中产生了第一批血细胞。Iturri等人现在展示了在定植胎儿肝脏之前，该器官发生的局部决定性造血分化的程度，并证明了EMPs独立于造血干细胞产生巨核形成的直接途径的存在。
The extra-embryonic yolk sac contains the first definitive multipotent hematopoietic cells, denominated erythromyeloid progenitors. They originate in situ prior to the emergence of hematopoietic stem cells and give rise to erythroid, monocytes, granulocytes, mast cells and macrophages, the latter in a Myb transcription factor-independent manner. We uncovered here the heterogeneity of yolk sac erythromyeloid progenitors, at the single cell level, and discriminated multipotent from committed progenitors, prior to fetal liver colonization. We identified two temporally distinct megakaryocyte differentiation pathways. The first occurs in the yolk sac, bypasses intermediate bipotent megakaryocyte-erythroid progenitors and, similar to the differentiation of macrophages, is Myb-independent. By contrast, the second originates later, from Myb-dependent bipotent progenitors expressing Csf2rb and colonize the fetal liver, where they give rise to megakaryocytes and to large numbers of erythrocytes. Understanding megakaryocyte development is crucial as they play key functions during vascular development, in particular in separating blood and lymphatic networks. EMP produce locally committed progenitors prior to fetal liver colonization Two sequential waves of EMP differentiation revealed at the single cell level Yolk sac Mk develop mainly from EMPs in a Myb-independent manner CD131 identifies Myb-dependent EMP-derived MEP progenitors in the yolk sac The yolk sac produces the first blood cells during embryonic development. Iturri et al. now show the extent of local definitive hematopoietic differentiation occurring in this organ before colonization of the fetal liver and demonstrate the existence of a direct pathway of megakaryopoiesis produced by EMPs, independently of hematopoietic stem cells.
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DOI：
10.1126/science.1247651
发表时间：
2014-02-14
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Jaitin DA;Kenigsberg E;Keren-Shaul H;Elefant N;Paul F;Zaretsky I;Mildner A;Cohen N;Jung S;Tanay A;Amit I
通讯作者：
Amit I
影响因子：
64.8
作者：
Gomez Perdiguero E;Klapproth K;Schulz C;Busch K;Azzoni E;Crozet L;Garner H;Trouillet C;de Bruijn MF;Geissmann F;Rodewald HR
通讯作者：
Rodewald HR
影响因子：
8.8
作者：
McGrath KE;Frame JM;Fegan KH;Bowen JR;Conway SJ;Catherman SC;Kingsley PD;Koniski AD;Palis J
通讯作者：
Palis J
影响因子：
4.6
作者：
Kasaai B;Caolo V;Peacock HM;Lehoux S;Gomez-Perdiguero E;Luttun A;Jones EA
通讯作者：
Jones EA
影响因子：
24.8
作者：
Drissen, Roy;Thongjuea, Supat;Nerlov, Claus
通讯作者：
Nerlov, Claus