During embryonic development, blood cells emerge from specialized endothelial cells, named haemogenic endothelial cells (HECs). As HECs are rare and only transiently found in early developing embryos, it remains difficult to distinguish them from endothelial cells. Here we performed transcriptomic analysis of 28- to 32-day human embryos and observed that the expression of Fc receptor CD32 (FCGR2B) is highly enriched in the endothelial cell population that contains HECs. Functional analyses using human embryonic and human pluripotent stem cell-derived endothelial cells revealed that robust multilineage haematopoietic potential is harboured within CD32⁺ endothelial cells and showed that 90% of CD32⁺ endothelial cells are bona fide HECs. Remarkably, these analyses indicated that HECs progress through different states, culminating in FCGR2B expression, at which point cells are irreversibly committed to a haematopoietic fate. These findings provide a precise method for isolating HECs from human embryos and human pluripotent stem cell cultures, thus allowing the efficient generation of haematopoietic cells in vitro.

在胚胎发育过程中，血细胞从特殊的内皮细胞中产生，称为造血内皮细胞（HEC）。由于 HEC 非常罕见，并且仅在早期发育的胚胎中短暂存在，因此仍然很难将它们与内皮细胞区分开来。在这里，我们对 28 至 32 天的人类胚胎进行了转录组分析，观察到 Fc 受体 CD32 ( FCGR2B ) 的表达在含有 HEC 的内皮细胞群中高度富集。使用人胚胎和人多能干细胞衍生的内皮细胞进行的功能分析表明，CD32 ⁺内皮细胞具有强大的多谱系造血潜力，并表明 90% 的 CD32 ⁺内皮细胞是真正的 HEC。值得注意的是，这些分析表明 HEC 经历不同的状态，最终表达FCGR2B，此时细胞不可逆转地走向造血命运。这些发现提供了一种从人类胚胎和人类多能干细胞培养物中分离HEC的精确方法，从而可以在体外有效生成造血细胞。