PDF(Pubmed)
Abstract：
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.
摘要：
人类造血从卵黄囊早期开始，并在发育过程中经历特定部位和阶段的变化。造血个体发育中性质变化的内在机制仍然知之甚少。这里,我们分析了人类原发性造血干/祖细胞（HSPCs）在不同发育阶段的单细胞转录组，包括卵黄囊（YS），AGM,胎儿肝脏（FL），脐带血(UCB)和成人外周血(PB)动员HSPCs。这些特定阶段的HSPC表现出不同的内在特性，比如新陈代谢，自我更新,区分潜力等。然后，我们生成了高度相关的基因调控网络（GRN）模块，这些模块是差异HSC关键属性的基础。特别是,我们确定了控制淋巴潜能的GRN和关键调节因子，人HSC的自我更新和有氧呼吸。引入选定的调节剂可促进源自人多能干细胞的HSPC中的关键HSC功能。因此,作为人HSC的关键内在特性的基础的GRN提供了在体外产生全功能HSC的有价值的指导。
