Abstract：
Hematopoietic stem cell (HSC)-independent lymphopoiesis has been elucidated in murine embryos. However, our understanding regarding human embryonic counterparts remains limited. Here, we demonstrated the presence of human yolk sac-derived lymphoid-biased progenitors (YSLPs) expressing CD34, IL7R, LTB, and IRF8 at Carnegie stage 10, much earlier than the first HSC emergence. The number and lymphopoietic potential of these progenitors were both significantly higher in the yolk sac than the embryo proper at this early stage. Importantly, single-cell/bulk culture and CITE-seq have elucidated the tendency of YSLP to differentiate into innate lymphoid cells and dendritic cells. Notably, lymphoid progenitors in fetal liver before and after HSC seeding displayed distinct transcriptional features, with the former closely resembling those of YSLPs. Overall, our data identified the origin, potential, and migratory dynamics of innate lymphoid-biased multipotent progenitors in human yolk sac before HSC emergence, providing insights for understanding the stepwise establishment of innate immune system in humans.
摘要：
已在鼠胚胎中阐明了造血干细胞（HSC）非依赖性淋巴细胞生成。然而,我们对人类胚胎对应物的理解仍然有限。这里,我们证明了人类卵黄囊衍生的淋巴样偏向祖细胞（YSLPs）表达CD34，IL7R，LTB,和IRF8在卡内基第10阶段，比第一次HSC出现要早得多。在此早期，卵黄囊中这些祖细胞的数量和淋巴生成潜力均显着高于适当的胚胎。重要的是,单细胞/批量培养和CITE-seq阐明了YSLP向先天淋巴样细胞和树突状细胞分化的趋势。值得注意的是,HSC接种前后胎儿肝脏中的淋巴祖细胞显示出不同的转录特征，前者与YSLP非常相似。总的来说,我们的数据确定了起源，潜力，在HSC出现之前，人类卵黄囊中先天淋巴样偏向多能祖细胞的迁移动力学，为理解人类先天免疫系统的逐步建立提供见解。
