多能干細胞產生的先天淋巴樣細胞的鑒定和表征

2022年11月1日，中國科學院廣州生物醫藥與健康研究院生命科學聯合學院，中國科學院再生生物學重點實驗室，生物土地實驗室(廣州再生醫學與衛生廣東省實驗室)，中國科學院大學（CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health,

ChineseAcademy of Sciences, Guangzhou Medical University, Guangzhou 510530, ChinaBioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou 510005, ChinaUniversity of Chinese Academy of Sciences, Beijing 100049, China） Mengyun Zhang 研究團隊在《Cell Reports》，發表論文，標題為：“Identification and characterization of innate lymphoid cells generated from pluripotent stem cells”

“多能干細胞產生的先天淋巴樣細胞的鑒定和表征”

Abstract

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 Rag2-/-Il2rg-/- 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.

摘要

先天淋巴樣細胞(ILCs)在調節組織穩態和先天免疫應答中起著重要作用。多能干細胞(PSC)來源的造血祖細胞(iHPCs)移植后產生的ILCs尚未有報道。在這里，我們證明了在Runx1和Hoxa9表達引導下，Rag2-/- il2rg -/-受體植入psc衍生的iHPCs中存在ILCs。移植后，iHPCs立即在骨髓中產生含有常見輔助性ILC祖細胞的ILC相關祖細胞，隨后是被稱為ILC祖細胞的更有限的群體，它們能夠在原發性和繼發性免疫缺陷受體中進一步分化為成熟的ILC。psc衍生的ILCs具有多種組織分布和正常的免疫功能。單細胞轉錄組學揭示了psc衍生的ILCs在體內的發育軌跡，這與天然ILCs的發育軌跡一致。我們的研究為移植psc來源的iHPCs作為細胞源的動物中ILCs的產生提供了見解。

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