Early development and functional properties of tryptase/chymase double-positive mast cells from human pluripotent stem cells. (30th October 2020)

• Record Type: Journal Article
• Authors: Bian, Guohui; Gu, Yanzheng; Xu, Changlu; Yang, Wenyu; Pan, Xu; Chen, Yijin; Lai, Mowen; Zhou, Ya; Dong, Yong; Mao, Bin; Zhou, Qiongxiu; Chen, Bo; Nakathata, Tatsutoshi; Shi, Lihong; Wu, Min; Zhang, Yonggang; Ma, Feng
• Editors: Li, Jinsong
• Is Part Of: Journal of molecular cell biology. Volume 13:Number 2(2021)
• Page Start: 104
• Page End: 115
• Publication Date: 2020-10-30
• Subjects: mast cells -- human pluripotent stem cells (hPSCs) -- development -- tryptase -- chymase; Molecular biology -- Periodicals; 571.605
• DOI: 10.1093/jmcb/mjaa059
• Languages: English
• ISSNs: 1674-2788

Abstract

Abstract: 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 (MCTC s). 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, MCTC s 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 MCTC s could play a central role in tumor immunity. These findings could help elucidate the mechanisms controlling early development of MCTC s and have significant therapeutic implications.