在胚胎发生期间,在自我更新的造血干细胞(HSC)出现之前,造血祖细胞的波从造血内皮(HE)发展。尽管以前的研究表明卵黄囊来源的红骨髓祖细胞和HSC来自不同的HE群体,尚不清楚最早的淋巴能力祖细胞,多能祖细胞,HSC来源于普通HE。在这项研究中,我们通过克隆试验和单细胞转录组学研究证明,在早期鼠胚胎中具有功能性HSC潜能的罕见HE与不能产生HSC的具有多谱系造血潜能的更丰富HE不同.具体来说,具有HSC能力的HE的特征在于CXCR4表面标志物的表达和与调节HSC休眠和自我更新的动脉程序相关的基因的较高表达。一起来看,这些发现提示了发育造血的修正模型,其中多能祖细胞和HSC的初始群体独立于HE产生,具有不同的表型和转录特性.
During embryogenesis, waves of hematopoietic progenitors develop from hemogenic endothelium (HE) prior to the emergence of self-renewing hematopoietic stem cells (HSCs). Although previous studies have shown that yolk-sac-derived erythromyeloid progenitors and HSCs emerge from distinct populations of HE, it remains unknown whether the earliest lymphoid-competent progenitors, multipotent progenitors, and HSCs originate from common HE. In this study, we demonstrate by clonal assays and single-cell transcriptomics that rare HE with functional HSC potential in the early murine embryo are distinct from more abundant HE with multilineage hematopoietic potential that fail to generate HSCs. Specifically, HSC-competent HE are characterized by expression of CXCR4 surface marker and by higher expression of genes tied to arterial programs regulating HSC dormancy and self-renewal. Taken together, these findings suggest a revised model of developmental hematopoiesis in which the initial populations of multipotent progenitors and HSCs arise independently from HE with distinct phenotypic and transcriptional properties.