Early development and functional properties of tryptase/chymase double-positive mast cells from human pluripotent stem cells  

作　　者：Guohui Bian Yanzheng Gu Changlu Xu Wenyu Yang Xu Pan Yijin Chen Mowen Lai Ya Zhou Yong Dong Bin Mao Qiongxiu Zhou Bo Chen Tatsutoshi Nakathata Lihong Shi Min Wu Yonggang Zhang Feng Ma 

机构地区：[1]Center for Stem Cell Research and Application,Institute of Blood Transfusion,Chinese Academy of Medical Sciences&Peking Union Medical College(CAMS&PUMC),Chengdu 610052,China [2]State Key Laboratory of Experimental Hematology,National Clinical Research Center for Blood Diseases,Institute of Hematology&Blood Diseases Hospital,CAMS&PUMC,Tianjin 300020,China [3]Stem Cell Key Laboratory of Jiangsu Province,Institute of Medical Biotechnology,Suzhou University,Suzhou 215123,China [4]Center for iPS Cell Research and Application(CiRA),Kyoto University,Kyoto 606-8507,Japan [5]Department of Biomedical Sciences,School of Medicine and Health Sciences,University of North Dakota,Grand Forks,ND 58203,US

出　　处：《Journal of Molecular Cell Biology》2021年第2期104-115,共12页分子细胞生物学报（英文版）

基　　金：This work was supported by the National Basic Research Program(973 Program;2015CB96A902);the National Natural Science Foundation of China(H81170466 and H81370597);and the CAMS Initiatives for Innovative Medicine(2016-I2M-1-018)awarded to F.M.;the CAMS Initiatives for Innovative Medicine(2017-12M-2005);the Union Youth Fund of Chinese Academy of Medical Sciences(81572089)to G.B.;and the National Nature Science Foundation of China Youth Fund(81700107)to B.M.

摘　　要：Mast cells (MCs) play a pivotal role in the hypersensitivity reaction by regulating the innate and adaptive immune responses. Humans have two types of MCs. The first type, termed MCTC, is found in the skin and other connective tissues and expresses both tryptase and chymase, while the second, termed MCT, which only expresses tryptase, is found primarily in the mucosa. MCs induced from human adult-type CD34+ cells are reported to be of the MCT type, but the development of MCs during embryonic/fetal stages is largely unknown. Using an efficient coculture system, we identified that a CD34+c-kit+ cell population, which appeared prior to the emergence of CD34+CD45+ hematopoietic stem and progenitor cells (HSPCs), stimulated robust production of pure Tryptase+Chymase+ MCs (MCTCs). Single-cell analysis revealed dual development directions of CD34+c-kit+ progenitors, with one lineage developing into erythro-myeloid progenitors (EMP) and the other lineage developing into HSPC. Interestingly, MCTCs derived from early CD34+c-kit+ cells exhibited strong histamine release and immune response functions. Particularly, robust release of IL-17 suggested that these early developing tissue-type MCTCs could play a central role in tumor immunity. These findings could help elucidate the mechanisms controlling early development of MCTCs and have significant therapeutic implications.

关 键 词：mast cells human pluripotent stem cells(hPSCs) development TRYPTASE CHYMASE 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]