PDGFRbeta+ cells play a dual role as hematopoietic precursors and niche cells during mouse ontogeny

Hematopoietic stem cell (HSC) generation in the aorta-gonads-mesonephros region requires HSC specification signals from the surrounding microenvironment. In zebrafish, PDGF-B/PDGFRbeta 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/PDGFRbeta is involved. Here we show that PDGFRbeta is expressed in distinct perivascular stromal cell layers surrounding the mid-gestation dorsal aorta, and its deletion impairs hematopoiesis. We demonstrate that PDGFRbeta+ cells play a dual role in murine hematopoiesis. They act in the aortic niche to support HSPCs, and in addition, PDGFRbeta+ embryonic precursors give rise to a subset of HSPCs that persist into adulthood. These findings provide crucial information for the controlled production of these clinically important cells in vitro. Single-cell transcriptome profiling of E11 AGM samples from PDGFRB +/+ (WT) (n=1) and PDGFRB -/- (KO) (n=1) mice主动脉-性腺-中肾区的造血干细胞（Hematopoietic stem cell, HSC）生成，依赖于周围微环境提供的HSC特化信号。在斑马鱼中，血小板衍生生长因子-B/血小板衍生生长因子受体β（PDGF-B/PDGFRbeta）信号通路可调控造血干/祖细胞（hematopoietic stem/progenitor cell, HSPC）的生成，且是造血干细胞特化龛所必需的。目前对于体内小鼠造血干/祖细胞的特化过程，以及PDGF-B/PDGFRbeta是否参与其中，仍知之甚少。本研究发现，血小板衍生生长因子受体β（PDGFRbeta）在妊娠中期背主动脉周围的不同血管周围基质细胞层中表达，其基因敲除会损害小鼠的造血功能。我们证实，PDGFRβ阳性细胞在小鼠造血过程中发挥双重功能：一方面于主动脉龛内支持造血干/祖细胞的生成；另一方面，PDGFRβ阳性的胚胎前体细胞可分化为部分造血干/祖细胞，这些细胞可存活至成年阶段。上述研究结果为体外可控制备这类临床重要的造血细胞提供了关键理论依据。本研究对PDGFRB野生型（WT，n=1）与PDGFRB敲除型（KO，n=1）小鼠的E11天主动脉-性腺-中肾区样本开展了单细胞转录组谱分析。