Xie Xiaowei, Gou Fanglin, Zheng Zhaofeng, Zhang Yawen, Zhang Yingchi, Dong Fang, 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 & Peking Union Medical College, Tianjin 300020, China.
Tianjin Institutes of Health Science, Tianjin 301600, China.
iScience. 2024 Jul 3;27(8):110445. doi: 10.1016/j.isci.2024.110445. eCollection 2024 Aug 16.
Bone marrow (BM) is the dominant site of hematopoiesis after 20 post-conception weeks (PCWs), but the intricacies of hematopoietic development in fetal BM up to birth and its involvement in malignancies remain unknown. Here, we compared the single-cell transcriptomic profile of BM hematopoietic stem and progenitor cells (HSPCs) at the early (12-14 PCW), middle (19-22 PCW) second trimester, and the neonatal stage. The stemness of hematopoietic stem cell and multipotent progenitor (HSC/MPP) is established at the middle second trimester, then maintained until birth. Furthermore, differentiation potentials toward three lineages are enhanced after the middle second trimester for birth, accompanied by the upregulation of aerobic metabolism. Notably, decreased stemness in HSCs/MPPs and higher interferon signals in progenitors at the early second trimester rendered the HSPCs more proximal to leukemogenesis. Collectively, our work elucidated the dynamics of fetal hematopoiesis in preparation for birth, offering valuable insights into the pathological processes underlying leukemia.
骨髓（BM）是孕20周后造血的主要部位，但胎儿骨髓直至出生时造血发育的复杂性及其与恶性肿瘤的关系仍不清楚。在这里，我们比较了孕中期早期（12 - 14孕周）、中期（19 - 22孕周）和新生儿期骨髓造血干细胞和祖细胞（HSPCs）的单细胞转录组图谱。造血干细胞和多能祖细胞（HSC/MPP）的干性在孕中期中期建立，然后维持到出生。此外，孕中期中期后向三个谱系的分化潜能增强以准备出生，同时有氧代谢上调。值得注意的是，孕中期早期HSCs/MPPs的干性降低以及祖细胞中较高的干扰素信号使HSPCs更接近白血病发生。总的来说，我们的工作阐明了为出生做准备的胎儿造血动力学，为白血病潜在的病理过程提供了有价值的见解。
