动物造模,人类造血干细胞 z-bio 2022-10-26 746

　　Researchers such as Hanna K. A. Mikkola and Vincenzo Calvanese of the University of California, Los Angeles, collaborated to map human hematopoietic stem cells from the hematopoietic endothelium to birth.

　　Researchers created a single-cell transcriptomic map of human hematopoietic tissue, from earliest gestation to birth, and found that the hematopoietic stem cell (HSC) signature RUNX1+HOXA9+MLLT3+MECOM+HLF+SPINK2+ differentiates HSCs from progenitors throughout pregnancy Come on. In addition to the aorta-gonad-spleen region, nascent HSCs reproduced in the placenta and yolk sac before colonizing the liver at 6 weeks. Comparing HSCs at different stages of maturation, the researchers found that HSCs' transcription factor machinery is established after HSCs emerge, while their surface phenotypes change throughout development. The transition of HSCs to the liver marks a molecular transition in which surface antigens reflecting the identity of nascent HSCs are suppressed and the maturation hallmarks of HSCs, CD133 (encoded by PROM1) and HLA-DR, are acquired. The origin of HSCs was traced to ALDH1A1+KCNK17+ hemoblasts, which were derived from a subpopulation of IL33+ALDH1A1+ arterial endothelial cells called prehemoblasts.

　　Using spatial transcriptomics and immunofluorescence, the researchers saw this process in a population of hematopoietic cells within the aorta located in the abdominal cavity. Human HSC developmental atlas validates definitive aorta-gonad-kidney-like HSCs and progenitors generated from human pluripotent stem cells and serves as a guide for improving their maturation into functional HSCs.

　　It is understood that the developmental process of human HSCs is poorly defined due to the inability to determine when hematopoietic stem cells emerge and mature at different hematopoietic sites.