Zheng Zhaofeng, He Han, Tang Xinyu Thomas, Zhang Han, Gou Fanglin, Yang Hua, Cao Jiaxuan, Shi Shujuan, Yang Zining, Sun Guohuan, Xie Xiaowei, Zeng Yang, Wen Aiqing, Lan Yu, Zhou Jiaxi, Liu Bing, Zhou Bo O, Cheng Tao, Cheng Hui
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China; CAMS Center for Stem Cell Medicine, PUMC Department of Stem Cell and Regenerative Medicine, Tianjin, China.
Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China.
Cell Stem Cell. 2022 Nov 3;29(11):1562-1579.e7. doi: 10.1016/j.stem.2022.10.005.
During fetal development, human hematopoietic stem cells (HSCs) colonize the bone marrow (BM), where they self-renew and sustain hematopoiesis throughout life; however, the precise timepoint at which HSCs seed the BM is unclear. We used single-cell RNA-sequencing to map the transcriptomic landscape of human fetal BM and spleen hematopoietic stem/progenitor cells (HSPCs) and their microenvironment from 10 to 14 post-conception weeks (PCWs). We further demonstrated that functional HSCs capable of reconstituting long-term multi-lineage hematopoiesis in adult NOG mice do not emerge in the BM until 12 PCWs. In contrast, functional HSCs were not detected in the spleen by 14 PCWs. By comparing the niche-HSPC interactions between BM and spleen, we identified ligand-receptor pairs likely to be involved in fetal HSC migration and maintenance. Our work paves the way for research into the mechanisms underlying HSC colonization in human fetal BM and provides invaluable resources for future studies on HSC development.
在胎儿发育过程中，人类造血干细胞（HSCs）定殖于骨髓（BM），在那里它们自我更新并维持终生造血；然而，HSCs定殖于BM的精确时间点尚不清楚。我们使用单细胞RNA测序来绘制人类胎儿BM和脾脏造血干/祖细胞（HSPCs）及其微环境在受孕后10至14周（PCWs）的转录组图谱。我们进一步证明，能够在成年NOG小鼠中重建长期多谱系造血的功能性HSCs直到12 PCWs才在BM中出现。相比之下，到14 PCWs时在脾脏中未检测到功能性HSCs。通过比较BM和脾脏之间的微环境与HSPCs的相互作用，我们确定了可能参与胎儿HSC迁移和维持的配体-受体对。我们的工作为研究人类胎儿BM中HSC定殖的潜在机制铺平了道路，并为未来HSC发育研究提供了宝贵的资源。
