2021-06-03

法国巴斯德研究所Elisa Gomez Perdiguero小组揭示巨核细胞的生产来源。该研究成果于2021年5月31日在线发表在国际学术期刊《免疫》上。

胚胎卵黄囊含有第一种明确的多能造血细胞，叫做红系骨髓前体细胞。它们在出现造血干细胞之前原位起源，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转录因子非依赖的方式形成。

研究人员在单细胞水平发现了卵黄囊红系骨髓祖细胞的异质性，并在肝脏定植之前从确定的前体细胞中分辨出了多潜能性。研究人员鉴定了两种短暂不同的巨核细胞分化途径。第一次发生在卵黄囊中，绕过中间体双潜能的巨核细胞-红细胞前体细胞，类似于巨噬细胞的分化，是MyB无关的。相比之下，后来源自表达Csf2rb的MyB依赖性的双潜能前体细胞，并定植在胎儿肝脏，从而产生巨核细胞和大量的红细胞。

了解巨核细胞发育至关重要，因为它们在血管发育期间发挥关键功能，特别是在分离血液和淋巴结网络中。 

附：英文原文

Title: Megakaryocyte production is sustained by direct differentiation from erythromyeloid progenitors in the yolk sac until midgestation

Author: Lorea Iturri, Laina Freyer, Anne Biton, Pascal Dardenne, Yvan Lallemand, Elisa Gomez Perdiguero

Issue&Volume: 2021-05-31

Abstract: 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.

DOI: 10.1016/j.immuni.2021.04.026