Hematopoiesis at single cell resolution spanning human development and maturation

Hematopoiesis is a process of constitutive regeneration whereby hematopoietic stem and progenitor cells (HSPCs) constantly replenish mature blood cells. During maturation and aging, HSPCs alter their output to support the shifting demands of prenatal development and postnatal maturation both at homeostasis and in response to stress. How HSPC ontogeny changes throughout life is unknown; studies to date have largely focused on analysis of specific individual ages, particularly those done at single cell resolution. Here, we performed single cell RNA-seq of human HSPCs from early prenatal development into mature adulthood, demonstrating dynamic remodeling of HSPC transcriptional states and differentiation trajectories over time. We identified age-specific gene expression patterns of lineage commitment throughout human life, and developed an approach for identifying, prospectively purifying, and functionally validating age-specific HSPC states. Together, our findings define the temporal evolution of hematopoiesis during human development and maturation, and uncover principles applicable to age-biased blood diseases.