Platelet-derived growth factor receptor alpha (PDGFR alpha) is a dominant marker of mesodermal mesenchymal cells in mice. Previous studies demonstrated that PDGFR alpha-positive (PDGFR alpha+) mesodermal cells develop not only into mesenchymal cells but also into a subset of total hematopoietic cells (HCs) in the limited period during mouse embryogenesis. However, the precise characteristics of the PDGFRa lineage positive (PDGFR alpha Lin+) HCs in adult mouse hematopoiesis are largely unknown. In this study, we systematically evaluated the characteristics of PDGFR alpha Lin+ HCs in the bone marrow and peripheral blood using PDGFR alpha-CRE; ROSA(tdTomato) mice. Flow cytometry analysis revealed that PDGFR alpha Lin+ HCs accounted for approximately 20% of total HCs in both the bone marrow and peripheral blood in adult mice. Compositions of myeloid and lymphoid subpopulations among CD45+ mononuclear cells were almost identical in both PDGFR alpha Lin+ and PDGFR alpha Lin- cells. Single-cell RNA-sequencing analysis also demonstrated that the transcriptomic signatures of the PDGFR alpha Lin+ HCs in the peripheral blood largely overlapped with those of the PDGFR alpha Lin- HCs, suggesting equivalent functions of the PDGFR alpha Lin+ and PDGFR alpha Lin- HCs. Although pathophysiological activities of the PDGFR alpha Lin + HCs were not evaluated, our data clearly demonstrate a significant role of the PDGFR alpha Lin + HCs in physiological hematopoiesis in adult mice. (C) 2020 The Authors. Published by Elsevier Inc.