Hematopoietic stem cells (HSCs) mature from pre-HSCs that originate in the major arteries of the embryo. To identify HSCs from in vitro sources, it will be necessary to refine markers of HSCs matured ex vivo. We purified and compared the transcriptomes of pre-HSCs, HSCs matured ex vivo, and fetal liver HSCs. We found that HSC maturation in vivo or ex vivo is accompanied by the down-regulation of genes involved in embryonic development and vasculogenesis, and up-regulation of genes involved in hematopoietic organ development, lymphoid development, and immune responses. Ex vivo matured HSCs more closely resemble fetal liver HSCs than pre-HSCs, but are not their molecular equivalents. We show that ex vivo–matured and fetal liver HSCs express programmed death ligand 1 (PD-L1). PD-L1 does not mark all pre-HSCs, but cell surface PD-L1 was present on HSCs matured ex vivo. PD-L1 signaling is not required for engraftment of embryonic HSCs. Hence, up-regulation of PD-L1 is a correlate of, but not a requirement for, HSC maturation.

造血干细胞（HSC）从HSC之前成熟，起源于胚胎的主要动脉。为了从体外来源鉴定HSC，将有必要完善离体成熟HSC的标记。我们纯化并比较了HSC之前，离体成熟的HSC和胎肝HSC的转录组。我们发现体内或离体的HSC成熟伴随着胚胎发育和血管生成相关基因的下调，以及造血器官发育，淋巴样发育和免疫反应中涉及的基因的上调。离体成熟的HSC与HSC之前的胚胎肝HSC更相似，但不是它们的分子等效物。我们显示，离体成熟和胎儿肝脏HSCs表达程序性死亡配体1（PD-L1）。PD-L1并未标记所有HSC之前的版本，但离体成熟的HSC上存在细胞表面PD-L1。胚胎HSC的植入不需要PD-L1信号。因此，PD-L1的上调与HSC成熟有关，但并非必需。