Identification and characterization of innate lymphoid cells generated from pluripotent stem cells
Identification and characterization of innate lymphoid cells generated from pluripotent stem cells
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多能干细胞产生的先天淋巴细胞的鉴定和表征
DOI：
10.1016/j.celrep.2022.111569
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发表时间：
2022-11-01
期刊：
影响因子：
8.8
通讯作者：
Zhang，Mengyun
中科院分区：
文献类型：
--
作者：
Xiong，Jiapin;Zhao，Yalan;Zhang，Mengyun
先天淋巴样细胞（ILCs）在调节组织稳态和先天免疫应答中起着重要作用。多能干细胞（PSC）来源的造血祖细胞（iHPCs）移植后产生的ILCs尚未有报道。在这里，我们证明了ilc存在于rag2−/−Il2rg−/−受体中，通过runx1和hoxa9表达引导psc衍生的iHPCs移植。移植后，iHPCs立即在骨髓中产生含有常见辅助性ILC祖细胞的ILC相关祖细胞，随后是被称为ILC祖细胞的更有限的群体，它们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ILCs具有多种组织分布和正常的免疫功能。单细胞转录组学揭示了psc衍生ILCs在体内的发育轨迹，这与天然ILCs的发育轨迹一致。我们的研究为移植psc来源的iHPCs作为细胞源的动物中ILCs的产生提供了见解。
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 inRag2−/−Il2rg−/−recipients engrafted with PSC-derived iHPCs guided byRunx1andHoxa9expression. 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 ILCsin 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.