多能干細(xì)胞產(chǎn)生的先天淋巴樣細(xì)胞的鑒定和表征

2022年11月1日，中國(guó)科學(xué)院廣州生物醫(yī)藥與健康研究院生命科學(xué)聯(lián)合學(xué)院，中國(guó)科學(xué)院再生生物學(xué)重點(diǎn)實(shí)驗(yàn)室，生物土地實(shí)驗(yàn)室(廣州再生醫(yī)學(xué)與衛(wèi)生廣東省實(shí)驗(yàn)室)，中國(guó)科學(xué)院大學(xué)（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(tuán)隊(duì)在《Cell Reports》，發(fā)表論文，標(biāo)題為：“Identification and characterization of innate lymphoid cells generated from pluripotent stem cells”

“多能干細(xì)胞產(chǎn)生的先天淋巴樣細(xì)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(xì)胞(ILCs)在調(diào)節(jié)組織穩(wěn)態(tài)和先天免疫應(yīng)答中起著重要作用。多能干細(xì)胞(PSC)來(lái)源的造血祖細(xì)胞(iHPCs)移植后產(chǎn)生的ILCs尚未有報(bào)道。在這里，我們證明了在Runx1和Hoxa9表達(dá)引導(dǎo)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(chǎn)生含有常見(jiàn)輔助性ILC祖細(xì)胞的ILC相關(guān)祖細(xì)胞，隨后是被稱為ILC祖細(xì)胞的更有限的群體，它們能夠在原發(fā)性和繼發(fā)性免疫缺陷受體中進(jìn)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(xì)胞轉(zhuǎn)錄組學(xué)揭示了psc衍生的ILCs在體內(nèi)的發(fā)育軌跡，這與天然ILCs的發(fā)育軌跡一致。我們的研究為移植psc來(lái)源的iHPCs作為細(xì)胞源的動(dòng)物中ILCs的產(chǎn)生提供了見(jiàn)解。

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