Multipotent progenitors and hematopoietic stem cells arise independently from hemogenic endothelium in the mouse embryo.
Multipotent progenitors and hematopoietic stem cells arise independently from hemogenic endothelium in the mouse embryo.
复制标题
在小鼠胚胎中，多能祖细胞和造血干细胞独立于造血内皮产生。
DOI：
10.1016/j.celrep.2021.109675
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发表时间：
2021-09-14
期刊：
影响因子：
8.8
通讯作者：
Hadland B
中科院分区：
文献类型：
--
作者：
Dignum T;Varnum-Finney B;Srivatsan SR;Dozono S;Waltner O;Heck AM;Ishida T;Nourigat-McKay C;Jackson DL;Rafii S;Trapnell C;Bernstein ID;Hadland B
在胚胎发生过程中，在自我更新的造血干细胞（HSC）出现之前，造血祖细胞波从造血内皮（HE）发育而来。虽然先前的研究表明，卵黄囊衍生的红骨髓祖细胞和造血干细胞出现从不同的人群HE，它仍然是未知的，是否最早的淋巴细胞的祖细胞，多能祖细胞，造血干细胞起源于共同的HE。在这项研究中，我们通过克隆测定和单细胞转录组学证明，在早期小鼠胚胎中具有功能性HSC潜力的罕见HE与具有多谱系造血潜力的更丰富的HE不同，这些HE不能产生HSC。具体而言，HSC-感受态HE的特征在于CXCR 4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更高表达。两者合计，这些研究结果表明，一个修订后的模型的发育造血，其中多能祖细胞和造血干细胞的初始群体出现独立于HE具有不同的表型和转录特性。Dignum等人整合了多种单细胞方法，揭示了造血内皮细胞（HE）的免疫表型和转录特性，这些内皮细胞是第一批HSC的前体。他们鉴定了具有克隆多能造血潜能的HE群体，该群体与HSC感受态HE不同，并揭示了与HSC感受态相关的动脉相关转录程序。
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. Integrating multiple single-cell approaches, Dignum et al. reveal immunophenotypic and transcriptional properties of hemogenic endothelium (HE) that are precursors to the first HSCs. They identify a population of HE with clonal multipotent hematopoietic potential distinct from HSC-competent HE and uncover arterial-associated transcriptional programs linked to HSC competence.
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影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
影响因子：
64.8
作者：
Cao, Junyue;Spielmann, Malte;Shendure, Jay
通讯作者：
Shendure, Jay
影响因子：
5.9
作者：
Batsivari A;Rybtsov S;Souilhol C;Binagui-Casas A;Hills D;Zhao S;Travers P;Medvinsky A
通讯作者：
Medvinsky A
影响因子：
21.3
作者：
Ditadi A;Sturgeon CM;Tober J;Awong G;Kennedy M;Yzaguirre AD;Azzola L;Ng ES;Stanley EG;French DL;Cheng X;Gadue P;Speck NA;Elefanty AG;Keller G
通讯作者：
Keller G
影响因子：
16.6
作者：
Fang JS;Coon BG;Gillis N;Chen Z;Qiu J;Chittenden TW;Burt JM;Schwartz MA;Hirschi KK
通讯作者：
Hirschi KK