Bone marrow hemogenic endothelial cells contribute multilineage hematopoietic progenitors in adult mice

Abstract

During development, hematopoietic stem/progenitor cells (HSPCs) originate from a subset of hemogenic endothelial cells (ECs) through a process of endothelial-to-hematopoietic transition (EHT). This process is temporally restricted to short developmental windows and generates HSPC with distinct capabilities for hematopoiesis. Although it is generally thought that adult hematopoiesis is sustained by HSCs derived from hemogenic endothelium during development, some observations point to EHT persistence in the late fetus/perinatally. Here we use lineage tracking and bioinformatics analysis to assess the presence of hemogenic endothelial cells in the adult mouse. Our analysis identifies a subset of bone marrow-resident adult endothelial cells, characterized by the expression of VE-Cadherin and the transcription factor RUNX1, that produce CD45+ hematopoietic cells. This EHT generates hematopoietic progenitors, and mature myeloid and lymphoid cells in the adult mouse. Our results reveal the identification of a distinct source of adult blood.