Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, EH16 4TJ Edinburgh, UK; Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, 5 Little France Drive, EH16 4UU Edinburgh, UK.
Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, 5 Little France Drive, EH16 4UU Edinburgh, UK.
Cell Rep. 2022 Jul 19;40(3):111114. doi: 10.1016/j.celrep.2022.111114.
Hematopoietic stem cell (HSC) generation in the aorta-gonad-mesonephros region requires HSC specification signals from the surrounding microenvironment. In zebrafish, PDGF-B/PDGFRβ signaling controls hematopoietic stem/progenitor cell (HSPC) generation and is required in the HSC specification niche. Little is known about murine HSPC specification in vivo and whether PDGF-B/PDGFRβ is involved. Here, we show that PDGFRβ is expressed in distinct perivascular stromal cell layers surrounding the mid-gestation dorsal aorta, and its deletion impairs hematopoiesis. We demonstrate that PDGFRβ cells play a dual role in murine hematopoiesis. They act in the aortic niche to support HSPCs, and in addition, PDGFRβ embryonic precursors give rise to a subset of HSPCs that persist into adulthood. These findings provide crucial information for the controlled production of HSPCs in vitro.
造血干细胞(HSC)在主动脉-性腺-中肾区的生成需要来自周围微环境的 HSC 特异性信号。在斑马鱼中,PDGF-B/PDGFRβ 信号控制造血干细胞/祖细胞(HSPC)的生成,并且在 HSC 特异性龛位中是必需的。关于体内小鼠 HSPC 特异性及其是否涉及 PDGF-B/PDGFRβ 的知识很少。在这里,我们表明 PDGFRβ 在围绕中孕期背主动脉的不同血管周基质细胞层中表达,其缺失会损害造血。我们证明 PDGFRβ 细胞在小鼠造血中具有双重作用。它们在主动脉龛位中作用于 HSPCs,此外,PDGFRβ 胚胎前体产生一组在成年期持续存在的 HSPCs。这些发现为 HSPCs 的体外受控生成提供了重要信息。