Adult Connective Tissue-Resident Mast Cells Originate from Late Erythro-Myeloid Progenitors
Authors: Linrong Lu
Meng Xia
Xiang Zhang
Zhiqing Li
Qicong Shen
Lin Yi
Junfang Xu
Xuetao Cao
Dan Han
Juan Liu
Sheng Xu
Shuxun Liu
Journal: Immunity (2018)
Discipline: IMMUNOLOGY
Keywords: Erythro-myeloid progenitors; Hematopoietic stem cells; Mast cell-committed progenitors; Mast cells; Ontogeny
Affiliations: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China; National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai 200433, China., National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai 200433, China., Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China., Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China; National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai 200433, China; Department of Immunology & Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China; College of Life Science, Nankai University, Tianjin 300071, China. Electronic address: .

Abstract:  Tissue-resident mast cells are associated with many inflammatory and physiological processes. Although mast cells arise from the yolk sac, the exact ontogeny of adult mast cells remains unclear. Here we have investigated the hematopoietic origin of mast cells using fate-mapping systems. We have shown that early erythro-myeloid progenitors (EMPs), late EMPs, and definitive hematopoietic stem cells (HSCs) each gave rise to mast cells in succession via an intermediate integrin Œ≤7+ 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 and pleural cavity. Thus, mast cells with distinct origin displayed tissue-location preferences: early EMP-derived cells were limited to adipose and pleural cavity and late EMP-derived cells dominated most connective tissues, while HSC-derived cells were a main group in mucosa. Therefore, embryonic origin shapes the heterogeneity of adult mast cells, with diverse functions in immunity and development. 

Retracted: No

PubPeer comments:
 Figures 1C and S1A. Two flow cytometry panels that appear to be representing different experiments appear to share unexpected similarities. Here is an overview of the two figures with those panels marked in red.  And here is a detail of the two panels. The area marked in red here appears to be more similar than expected.  , 
 Sure, but both are skin, CD45.1 and CD117 staining. Can be the same sample shown twice for some purpose. , 
 Some cell flow cytometry diagrams are just very similar, but there are differences when you look carefully. For normal cell flow cytometry data, I think nobody could guarantee that every point or small group has its own identity. , 
 Some cell flow cytometry diagrams are just very similar, but there are differences when you look carefully. , 
  They are similar, but if we focus on the two circled areas I made, we can clearly see the dots in the left parts are different. , 
 Thank you for your comment. **Actually, Figure1C and S1A in this paper represent the same experiment in a complementary way**, aiming to address the reconstitution of mast cells in adult WT mice and Kit mutant mice after BMT.  Figure 1A bar graph showed the reconstitution of mast cells in different organs of adult WT mice (pooled data from 5 mice), **including the skin as indicated here in red**. Flow cytometry plots from one of the 5 WT recipient mice were selected to show the gating strategy during the analysis of mast cells (Figure S1A). Figure 1C showed that the skin mast cell reconstitution was also compared between WT mice and Kit mutant mice, and **the same skin sample from WT mice used in Figure S1A** was selected again as WT control to exactly compare with skin sample from Kit mutant mice. **The same skin sample was analyzed twice to show the mast cell reconstitution efficacy (Figure 1C) and show the analysis process (FACS gating strategy, Figure S1A) respectively. So, they look like similar.** The slight difference between the two panels was due to analysis at different time (Figure 1C: analyzed together with the skin sample from Kit mutant mice; Figure S1A: analyzed together with the samples from other organs of WT mice). ,