Identification and characterization of innate lymphoid cells generated from pluripotent stem cells

Jiapin Xiong; Yalan Zhao; Yunqing Lin; Lebei Chen; Qitong Weng; Chuanping Shi; Xiaofei Liu; Yang Geng; Lijuan Liu; Jinyong Wang; Mengyun Zhang

doi:10.1016/j.celrep.2022.111569

Identification and characterization of innate lymphoid cells generated from pluripotent stem cells

Cell Rep. 2022 Nov 1;41(5):111569. doi: 10.1016/j.celrep.2022.111569.

Authors

Jiapin Xiong¹, Yalan Zhao², Yunqing Lin³, Lebei Chen², Qitong Weng⁴, Chuanping Shi², Xiaofei Liu², Yang Geng², Lijuan Liu², Jinyong Wang⁵, Mengyun Zhang⁶

Affiliations

¹ 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.
² 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.
³ Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou 510005, China.
⁴ 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; University of Chinese Academy of Sciences, Beijing 100049, China.
⁵ 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. Electronic address: wang_jinyong@gibh.ac.cn.
⁶ 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. Electronic address: zhang_mengyun@gzhmu.edu.cn.

PMID: 36323259
DOI: 10.1016/j.celrep.2022.111569

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.

Keywords: CP: Developmental biology; CP: Immunology; Hoxa9; ILC progenitors; Runx1; differentiation; generation; innate lymphoid cells; pluripotent stem cells; single-cell RNA-seq.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation
Immunity, Innate*
Lymphocytes / metabolism
Lymphoid Progenitor Cells / metabolism
Pluripotent Stem Cells*