Delineating spatiotemporal and hierarchical development of human fetal innate lymphoid cells  

作　　者：Chen Liu Yandong Gong Han Zhang Hua Yang Yang Zeng Zhilei Bian Qian Xin Zhijie Bai Man Zhang Jian He Jing Yan Jie Zhou Zongcheng Li Yanli Ni Aiqing Wen Yu Lan Hongbo Hu Bing Liu 

机构地区：[1]State Key Laboratory of Proteomics,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing,China [2]State Key Laboratory of Experimental Hematology,Institute of Hematology,Fifth Medical Center of Chinese PLA General Hospital,Beijing,China [3]Department of Blood Transfusion,Daping Hospital,Army Military Medical University,Chongqing,China [4]Tianjin Central Hospital of Gynecology Obstetrics,Tianjin,China [5]Key Laboratory for Regenerative Medicine of Ministry of Education,Institute of Hematology,School of Medicine,Jinan University,Guangzhou,China [6]Center for Immunology and Hematology,the State Key Laboratory of Biotherapy,West China Hospital,Sichuan University.Collaboration and Innovation Center for Biotherapy,Chengdu,China

出　　处：《Cell Research》2021年第10期1106-1122,共17页细胞研究（英文版）

基　　金：This study was supported by grants from the National Key R&D Program of China(2020YFA0112400,2019YFA0110200,2017YFA0103401,2016YFA0100601 and 2016YFA0502203);the National Natural Science Foundation of China(31425012,31930054,31871173,81890991,82025002,81871232,81800102 and 81900115);the Program for Guangdong Introducing Innovative and Entrepreneurial Teams(2017ZT07S347);the Beijing Municipal Science&Technology Commission(Z171100000417009 and Beijing Leading Talents Program Z171100001117159);the State Key Laboratory of Proteomics(SKLP-K202003);the Key Research and Development Program of Guangdong Province(2019B020234002).

摘　　要：Whereas the critical roles of innate lymphoid cells(ILCs)in adult are increasingly appreciated,their developmental hierarchy in early human fetus remains largely elusive.In this study,we sorted human hematopoietic stem/progenitor cells,lymphoid progenitors,putative ILC progenitor/precursors and mature ILCs in the fetal hematopoietic,lymphoid and non-lymphoid tissues,from 8 to 12 post-conception weeks,for single-cell RNA-sequencing,followed by computational analysis and functional validation at bulk and single-cell levels.We delineated the early phase of ILC lineage commitment from hematopoietic stem/progenitor cells,which mainly occurred in fetal liver and intestine.We further unveiled interleukin-3 receptor as a surface marker for the lymphoid progenitors in fetal liver with T,B,ILC and myeloid potentials,while IL-3RA–lymphoid progenitors were predominantly B-lineage committed.Notably,we determined the heterogeneity and tissue distribution of each ILC subpopulation,revealing the proliferating characteristics shared by the precursors of each ILC subtype.Additionally,a novel unconventional ILC2 subpopulation(CRTH2–CCR9+ILC2)was identified in fetal thymus.Taken together,our study illuminates the precise cellular and molecular features underlying the stepwise formation of human fetal ILC hierarchy with remarkable spatiotemporal heterogeneity.

关 键 词：FETAL LYMPHOID INTESTINE 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]