Endothelial origin of hematopoietic stem cells: Insights from new technologies and unresolved questions

Xiaochen Ding1, Gaoke Liu2, Bing Liu3

  • 1State Key Laboratory of Experimental Hematology, Medical Innovation Research Department of PLA General Hospital, Beijing 100071, China.

Recent studies employing advanced technologies have supported the notion that definitive hematopoiesis, including the generation of hematopoietic stem cells (HSCs), originates from hemogenic endothelial cells (HECs). However, controversies persist regarding the nature, origin, and fate of HSC-generating HECs. This review synthesizes recent studies utilizing high-precision techniques, including single-cell transcriptomics, low-input epigenomics, and single-cell functional assays, to summarize advances in the enrichment markers, functional characteristics, and developmental trajectory of HSC-generating HECs. It further details the continuum nature of multiple refined cellular stages, ranging from the upstream arterial endothelial cells in the aorta as precursors of HECs to the downstream pre-hematopoietic stem cells. Additionally, this review addresses existing controversies by synthesizing relevant evidence and proposes directions and strategies for future research.

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