Li Fei, Zhu Yanling, Wang Tianyu, Tang Jun, Huang Yuhua, Gu Jiaming, Mai Yuchan, Wang Mingquan, Zhang Zhishuai, Ning Jiaying, Kang Baoqiang, Wang Junwei, Zhou Tiancheng, Cui Yazhou, Pan Guangjin
Key Laboratory of Immune Response and Immunotherapy, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical University, Guangzhou, 510530, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
Cell Regen. 2024 Apr 17;13(1):9. doi: 10.1186/s13619-024-00192-z.
Human hematopoiesis starts at early yolk sac and undergoes site- and stage-specific changes over development. The intrinsic mechanism underlying property changes in hematopoiesis ontogeny remains poorly understood. Here, we analyzed single-cell transcriptome of human primary hematopoietic stem/progenitor cells (HSPCs) at different developmental stages, including yolk-sac (YS), AGM, fetal liver (FL), umbilical cord blood (UCB) and adult peripheral blood (PB) mobilized HSPCs. These stage-specific HSPCs display differential intrinsic properties, such as metabolism, self-renewal, differentiating potentialities etc. We then generated highly co-related gene regulatory network (GRNs) modules underlying the differential HSC key properties. Particularly, we identified GRNs and key regulators controlling lymphoid potentiality, self-renewal as well as aerobic respiration in human HSCs. Introducing selected regulators promotes key HSC functions in HSPCs derived from human pluripotent stem cells. Therefore, GRNs underlying key intrinsic properties of human HSCs provide a valuable guide to generate fully functional HSCs in vitro.
人类造血始于早期卵黄囊，并在发育过程中经历特定部位和阶段的变化。造血个体发生过程中特性变化的内在机制仍知之甚少。在这里，我们分析了人类原代造血干细胞/祖细胞（HSPCs）在不同发育阶段的单细胞转录组，包括卵黄囊（YS）、主动脉-性腺-中肾区（AGM）、胎儿肝脏（FL）、脐带血（UCB）和成人外周血（PB）动员的HSPCs。这些阶段特异性的HSPCs表现出不同的内在特性，如代谢、自我更新、分化潜能等。然后，我们生成了与造血干细胞关键特性差异相关的高度共相关基因调控网络（GRNs）模块。特别是，我们确定了控制人类造血干细胞淋巴潜能、自我更新以及有氧呼吸的GRNs和关键调节因子。引入选定的调节因子可促进源自人类多能干细胞的HSPCs中的关键造血干细胞功能。因此，人类造血干细胞关键内在特性的GRNs为体外生成功能完全的造血干细胞提供了有价值的指导。
