CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China; Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou 510005, China; University of Chinese Academy of Sciences, Beijing 100049, China.
CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China.
Cell Rep. 2022 Nov 1;41(5):111569. doi: 10.1016/j.celrep.2022.111569.
Innate lymphoid cells (ILCs) play important roles in regulating tissue homeostasis and innate immune responses. Generation of ILCs after engraftment of pluripotent stem cell (PSC)-derived hematopoietic progenitors (iHPCs) has not yet been reported. Here, we document that ILCs exist in Rag2Il2rg recipients engrafted with PSC-derived iHPCs guided by Runx1 and Hoxa9 expression. Upon transplantation, iHPCs immediately give rise to ILC-related progenitors containing common helper ILC progenitors in the bone marrow, followed by a more restricted population named ILC progenitors, which are able to further differentiate into mature ILCs in the primary and secondary immunodeficient recipients. The PSC-derived ILCs exhibit multiple tissue distributions and normal immunological functions. Single-cell transcriptomics illustrates the developmental trajectory of PSC-derived ILCs in vivo, which is consistent with that of natural ILCs. Our study provides insights into the generation of ILCs in animals transplanted with PSC-derived iHPCs as a cell source.
先天淋巴细胞 (ILC) 在调节组织稳态和先天免疫反应方面发挥着重要作用。多能干细胞 (PSC) 衍生的造血祖细胞 (iHPC) 移植后产生 ILC 的情况尚未见报道。在这里，我们记录了在由 Runx1 和 Hoxa9 表达指导的 Rag2Il2rg 受体中存在 PSC 衍生的 iHPC 移植后存在 ILC。移植后，iHPC 立即在骨髓中产生含有共同辅助 ILC 祖细胞的 ILC 相关祖细胞，随后是更受限制的群体，称为 ILC 祖细胞，其能够在原发性和继发性免疫缺陷受体中进一步分化为成熟的 ILC。PSC 衍生的 ILC 具有多种组织分布和正常的免疫功能。单细胞转录组学说明了体内 PSC 衍生的 ILC 的发育轨迹，与天然 ILC 的轨迹一致。我们的研究为 PSC 衍生的 iHPC 作为细胞来源移植动物中 ILC 的产生提供了深入了解。
