Activation of lineage competence in hemogenic endothelium precedes the formation of hematopoietic stem cell heterogeneity.
Jun Xia, Mengyao Liu, Caiying Zhu, Shicheng Liu, Lanlan Ai, Dongyuan Ma, Ping Zhu, Lu Wang, Feng Liu
Author Information
Jun Xia: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Mengyao Liu: State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
Caiying Zhu: State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
Shicheng Liu: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Lanlan Ai: State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
Dongyuan Ma: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Ping Zhu: State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. ORCID
Lu Wang: State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. wanglu1@ihcams.ac.cn.
Feng Liu: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. liuf@ioz.ac.cn. ORCID
Hematopoietic stem and progenitor cells (HSPCs) are considered as a heterogeneous population, but precisely when, where and how HSPC heterogeneity arises remain largely unclear. Here, using a combination of single-cell multi-omics, lineage tracing and functional assays, we show that embryonic HSPCs originate from heterogeneous hemogenic endothelial cells (HECs) during zebrafish embryogenesis. Integrated single-cell transcriptome and chromatin accessibility analysis demonstrates transcriptional heterogeneity and regulatory programs that prime lymphoid/myeloid fates at the HEC level. Importantly, spi2 HECs give rise to lymphoid/myeloid-primed HSPCs (L/M-HSPCs) and display a stress-responsive function under acute inflammation. Moreover, we uncover that Spi2 is required for the formation of L/M-HSPCs through tightly controlling the endothelial-to-hematopoietic transition program. Finally, single-cell transcriptional comparison of zebrafish and human HECs and human induced pluripotent stem cell-based hematopoietic differentiation results support the evolutionary conservation of L/M-HECs and a conserved role of SPI1 (spi2 homolog in mammals) in humans. These results unveil the lineage origin, biological function and molecular determinant of HSPC heterogeneity and lay the foundation for new strategies for induction of transplantable lineage-primed HSPCs in vitro.
References
Bioinformatics. 2014 Aug 1;30(15):2114-20
[PMID: 24695404]
J Exp Med. 2017 Oct 2;214(10):2817-2827
[PMID: 28830909]
