Temporal molecular program of human hematopoietic stem and progenitor cells after birth

Hematopoietic stem and progenitor cells (HSPCs) give rise to the blood system and maintain hematopoiesis throughout the human lifespan. Here, we report a transcriptional census of human bone-marrow-derived HSPCs from the neonate, infant, child, adult, and aging stages, showing two subpopulations of multipotent progenitors separated by CD52 expression. From birth to the adult stage, stem and multipotent progenitors shared similar transcriptional alterations, and erythroid potential was enhanced after the infant stage. By integrating transcriptome, chromatin accessibility, and functional data, we further showed that aging hematopoietic stem cells (HSCs) exhibited a bias toward megakaryocytic differentiation. Finally, in comparison with the HSCs from the cord blood, neonate bone-marrow-derived HSCs were more quiescent and had higher long-term regeneration capability and durable self-renewal. Taken together, this work provides an integral transcriptome landscape of HSPCs and identifies their dynamics in post-natal steady-state hemopoiesis, thereby helping explore hematopoiesis in development and diseases. [Display omitted] •A comprehensive transcriptome census of HSPCs during human post-natal development•Two lineage-primed MPPs separated by CD52 expression•Erythroid enhancement in HSC/MPPs after infant and platelet bias in aging HSCs•Higher self-renewal of HSCs in neonate bone marrow than that in the cord blood Zhang et al. provided an integral transcriptomic analysis of HSPCs, defined their dynamics in post-natal steady-state hematopoiesis, and refined the heterogeneity of MPPs by CD52 expression. Neonate bone-marrow-derived HSCs exhibited higher reconstruction capability than cord blood HSCs. This resource will help understand hematopoiesis in development and disease.