Department of Stem Cell Therapy Science, Graduate School of Medicine, Osaka University, Suita, 565-0871, Japan.
Department of Stem Cell Therapy Science, Graduate School of Medicine, Osaka University, Suita, 565-0871, Japan; StemRIM Institute of Regeneration-Inducing Medicine, Osaka University, Suita, 565-0871, Japan.
Biochem Biophys Res Commun. 2021 Jan 1;534:186-192. doi: 10.1016/j.bbrc.2020.11.114. Epub 2020 Dec 11.
Platelet-derived growth factor receptor alpha (PDGFRα) is a dominant marker of mesodermal mesenchymal cells in mice. Previous studies demonstrated that PDGFRα-positive (PDGFRα+) 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 PDGFRα lineage positive (PDGFRα Lin+) HCs in adult mouse hematopoiesis are largely unknown. In this study, we systematically evaluated the characteristics of PDGFRα Lin+ HCs in the bone marrow and peripheral blood using PDGFRα-CRE; ROSA mice. Flow cytometry analysis revealed that PDGFRα 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 PDGFRα Lin+ and PDGFRα Lin- cells. Single-cell RNA-sequencing analysis also demonstrated that the transcriptomic signatures of the PDGFRα Lin+ HCs in the peripheral blood largely overlapped with those of the PDGFRα Lin- HCs, suggesting equivalent functions of the PDGFRα Lin+ and PDGFRα Lin- HCs. Although pathophysiological activities of the PDGFRα Lin + HCs were not evaluated, our data clearly demonstrate a significant role of the PDGFRα Lin + HCs in physiological hematopoiesis in adult mice.
血小板衍生生长因子受体α (PDGFRα) 是小鼠中中胚层间充质细胞的主要标志物。先前的研究表明,PDGFRα 阳性 (PDGFRα+) 间充质细胞不仅在胚胎发生的有限时期内发育为间充质细胞,而且发育为总造血细胞 (HCs) 的一个亚群。然而,成年小鼠造血中 PDGFRα 谱系阳性 (PDGFRα Lin+) HCs 的精确特征在很大程度上尚不清楚。在这项研究中,我们使用 PDGFRα-CRE; ROSA 小鼠系统地评估了骨髓和外周血中 PDGFRα Lin+ HCs 的特征。流式细胞术分析显示,PDGFRα Lin+ HCs 约占成年小鼠骨髓和外周血中总 HCs 的 20%。CD45+ 单核细胞中髓系和淋巴系亚群的组成在 PDGFRα Lin+ 和 PDGFRα Lin- 细胞中几乎相同。单细胞 RNA 测序分析还表明,外周血中 PDGFRα Lin+ HCs 的转录组特征与 PDGFRα Lin- HCs 的转录组特征大部分重叠,表明 PDGFRα Lin+ 和 PDGFRα Lin- HCs 具有等效的功能。虽然未评估 PDGFRα Lin+ HCs 的病理生理活性,但我们的数据清楚地表明 PDGFRα Lin+ HCs 在成年小鼠生理造血中具有重要作用。