Human hematopoiesis is a dynamic process that starts in utero 18–21 days post-conception. Understanding the site- and stage-specific variation in hematopoiesis is important if we are to understand the origin of hematological disorders, many of which occur at specific points in the human lifespan. To unravel how the hematopoietic stem/progenitor cell (HSPC) compartment changes during human ontogeny and the underlying gene regulatory mechanisms, we compare 57,489 HSPCs from 5 different tissues spanning 4 developmental stages through the human lifetime. Single-cell transcriptomic analysis identifies significant site- and developmental stage-specific transitions in cellular architecture and gene regulatory networks. Hematopoietic stem cells show progression from cycling to quiescence and increased inflammatory signaling during ontogeny. We demonstrate the utility of this dataset for understanding aberrant hematopoiesis through comparison to two cancers that present at distinct time points in postnatal life—juvenile myelomonocytic leukemia, a childhood cancer, and myelofibrosis, which classically presents in older adults.

人类造血是一个动态过程，在受孕后 18-21 天在子宫内开始。如果我们要了解血液疾病的起源，其中许多疾病发生在人类生命周期的特定阶段，那么了解造血作用的位点和阶段特异性变异非常重要。为了揭示造血干/祖细胞 (HSPC) 区室在人类个体发育过程中如何变化以及潜在的基因调控机制，我们比较了来自 5 个不同组织的 57,489 个 HSPC，跨越了人类一生的 4 个发育阶段。单细胞转录组分析可识别细胞结构和基因调控网络中重要的位点和发育阶段特异性转变。造血干细胞显示出从循环到静止的进展，并且在个体发育过程中炎症信号传导增加。我们通过与出生后不同时间点出现的两种癌症（幼年型粒单核细胞白血病（一种儿童癌症）和骨髓纤维化（通常出现在老年人中））进行比较，展示了该数据集在理解异常造血功能方面的实用性。