New frameworks for hematopoiesis derived from single-cell genomics

ABSTRACT: Recent advancements in single-cell genomics have enriched our understanding of hematopoiesis, providing intricate details about hematopoietic stem cell biology, differentiation, and lineage commitment. Technological advancements have highlighted extensive heterogeneity of cell populations and continuity of differentiation routes. Nevertheless, intermediate "attractor" states signify structure in stem and progenitor populations that link state transition dynamics to fate potential. We discuss how innovative model systems quantify lineage bias and how stress accelerates differentiation, thereby reducing fate plasticity compared with native hematopoiesis. We conclude by offering our perspective on the current model of hematopoiesis and discuss how a more precise understanding can translate to strategies that extend healthy hematopoiesis and prevent disease.