Prof. Xuetao Cao’s Group sheds new insight into the origin of connective tissue-resident mast cells


Prof. Xuetao Cao’s group published a research article in Immunity about the origin of connective tissue-resident mast cells (Zhiqing Li, Shuxun Liu, Junfang Xu, Xiang Zhang, Dan Han, Juan Liu, Meng Xia, Lin Yi, Qicong Shen, Sheng Xu, Linrong Lu & Xuetao Cao. Adult Connective Tissue-Resident Mast Cells Originate from Late Erythro-Myeloid Progenitors. Immunity 49, 1–14, October 16, 2018.).

Mast cells predominantly reside in tissues and are subclassified into two main subsets based on their tissue distribution: connective tissue mast cells (CTMCs) are located around venules and nerve endings in most connective tissues (i.e. skin, tongue, trachea, esophagus, adipose and peritoneal cavity); and mucosal mast cells (MMCs) are located inside the epithelia of the gut and respiratory mucosa. The prevailing dogma about mast cell ontogeny is that mast cells are constantly replenished from BM-derived mast cell progenitor(MCp). However these studies were based on the absent of mast cells. How the adult CTMC pool is maintained under steady state condition is unknown.

Prof. Xuetao Cao, PhD student Zhiqing Li and associate professor Shuxun Liu investigated the hematopoietic origin of mast cells using fate-mapping systems and showed that E7.5 early erythro-myeloid progenitors (EMPs) and E8.5 late EMPs in the yolk sac and E9.5 definitive hematopoietic stem cells (HSCs) within the aorta, gonads, and mesonephros region (AGM) each gave rise to mast cells in succession via an intermediate integrin b7+ progenitor. From late embryogenesis to adult, early EMP-derived mast cells were largely replaced by late EMP-derived cells in most connective tissues except adipose tissue and pleural cavity. Thus, mast cells with distinct origin displayed tissue-location preferences: early EMP-derived mast cells were limited to adipose and pleural cavity and late EMP-derived mast cells dominated most connective tissues, while HSC-derived mast cells were a main group in mucosa. Unlike MMCs which originate from E9.5 HSCs and depend on adult HSCs for their replacement, CTMCs originate from yolk sac-EMPs and are maintained independently of adult HSCs throughout life.

This work delineates the origin and development route of mast cells. It also raises several areas for future investigation: identifying the master transcription factors that direct mast cell differentiation from distinct origin; elucidating the mechanisms underlying their tissue preferences and metachromatic granule generation after they reside in tissues and the physiological functions of mast cells during embryonic development.