Redefining hematopoietic progenitor cells and reforming the hierarchy of hematopoiesis

Abstract

SummaryDeciphering the mechanisms underlying progenitor cell definition and fate decisions is critical to answering fundamental questions regarding hematopoietic lineage commitment. Here, we redefine the entire spectrum of original hematopoietic progenitor cells (HPCs) using a comprehensive transcriptional atlas, effectively subverting the conventional definition of HPCs. We have defined the transcription factors associated with the key fate decisions at each level of the hematopoietic hierarchy, providing additional insights into the underlying molecular mechanisms. Initial hematopoietic progenitors are simultaneously primed into erythroid, lymphoid, and neutrophilic progenitors during the first differentiation stage of hematopoiesis. Moreover, plasma progenitor cells were identified and defined. A hematopoietic hierarchy roadmap was reformed, demonstrating that the megakaryocytic–erythroid lineage commitment process is continuous. However, the lymphoid lineage commitment process was identified as a discrete stepwise process with distinct lineage-committed populations during hematopoiesis. Our study has revealed numerous possibilities for precisely controlling progenitor cell differentiation, facilitating research development in regenerative medicine and disease treatment.HighlightsHematopoietic progenitors are redefined using comprehensive transcriptional atlasFate decision-related transcription factors are revealed in the hematopoietic hierarchyProgenitor lineage commitment includes continuous and stepwise processesThe hierarchy of hematopoiesis was reformed