Ning Xiaowei, Du Junjie, Gong Yandong, Yao Yingpeng, Bai Zhijie, Ni Yanli, Li Yanyan, Li Zongcheng, Zhao Haixin, Zhou Jie, Liu Bing, Lan Yu, Hou Siyuan
State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China.
Chinese PLA Medical School, Chinese PLA General Hospital, Beijing 100853, China; State Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Institute of Hematology, Senior Department of Hematology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100071, China.
J Genet Genomics. 2023 Sep;50(9):661-675. doi: 10.1016/j.jgg.2023.05.006. Epub 2023 May 23.
Prior to the generation of hematopoietic stem cells (HSCs) from the hemogenic endothelial cells (HECs) mainly in the dorsal aorta in midgestational mouse embryos, multiple hematopoietic progenitors including erythro-myeloid progenitors and lymphoid progenitors are generated from yolk sac HECs. These HSC-independent hematopoietic progenitors have recently been identified as major contributors to functional blood cell production until birth. However, little is known about yolk sac HECs. Here, combining integrative analyses of multiple single-cell RNA-sequencing datasets and functional assays, we reveal that Neurl3-EGFP, in addition to marking the continuum throughout the ontogeny of HSCs from HECs, can also serve as a single enrichment marker for yolk sac HECs. Moreover, while yolk sac HECs have much weaker arterial characteristics than either arterial endothelial cells in the yolk sac or HECs within the embryo proper, the lymphoid potential of yolk sac HECs is largely confined to the arterial-biased subpopulation featured by the Unc5b expression. Interestingly, the B lymphoid potential of hematopoietic progenitors, but not for myeloid potentials, is exclusively detected in Neurl3-negative subpopulations in midgestational embryos. Taken together, these findings enhance our understanding of blood birth from yolk sac HECs and provide theoretical basis and candidate reporters for monitoring step-wise hematopoietic differentiation.
在妊娠中期小鼠胚胎主要位于背主动脉的造血内皮细胞（HECs）产生造血干细胞（HSCs）之前，卵黄囊HECs会产生多种造血祖细胞，包括红系-髓系祖细胞和淋巴系祖细胞。这些不依赖HSC的造血祖细胞最近被确定为出生前功能性血细胞产生的主要贡献者。然而，关于卵黄囊HECs的了解却很少。在这里，通过结合多个单细胞RNA测序数据集的综合分析和功能测定，我们发现Neurl3-EGFP除了标记从HECs到HSCs整个个体发育过程的连续性外，还可以作为卵黄囊HECs的单一富集标记。此外，虽然卵黄囊HECs的动脉特征比卵黄囊中动脉内皮细胞或胚胎本身的HECs弱得多，但卵黄囊HECs的淋巴系潜能主要局限于以Unc5b表达为特征的动脉偏向亚群。有趣的是，在妊娠中期胚胎的Neurl3阴性亚群中仅检测到造血祖细胞的B淋巴系潜能，而未检测到髓系潜能。综上所述，这些发现加深了我们对卵黄囊HECs产生血液的理解，并为监测逐步造血分化提供了理论基础和候选报告基因。
