Open AccessSingle‐cell transcriptomes of mouse bladder urothelium uncover novel cell type markers and urothelial differentiation characteristics
Author(s) -
Li Yan,
Liu Yaxiao,
Gao Zhengdong,
Zhang Lekai,
Chen Lipeng,
Wu Zonglong,
Liu Qinggang,
Wang Shuai,
Zhou Nan,
Chai Toby C.,
Shi Benkang
Publication year - 2021
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.13007
Subject(s) - urothelium , urothelial cell , biology , urinary bladder , cell type , cell , transcriptome , pathology , urinary system , gene expression , gene , medicine , anatomy , genetics
Abstract Objectives Much of the information to date in terms of subtypes and function of bladder urothelial cells were derived from anatomical location or by the expression of a small number of marker genes. To have a comprehensive map of the cellular anatomy of bladder urothelial cells, we performed single‐cell RNA sequencing to thoroughly characterize mouse bladder urothelium. Materials and methods A total of 18,917 single cells from mouse bladder urothelium were analysed by unbiased single‐cell RNA sequencing. The expression of the novel cell marker was confirmed by immunofluorescence using urinary tract infection models. Results Unsupervised clustering analysis identified 8 transcriptionally distinct cell subpopulations from mouse bladder urothelial cells. We discovered a novel type of bladder urothelial cells marked by Plxna4 that may be involved with host response and wound healing. We also found a group of basal‐like cells labelled by ASPM that could be the progenitor cells of adult bladder urothelium. ASPM + urothelial cells are significantly increased after injury by UPEC. In addition, specific transcription factors were found to be associated with urothelial cell differentiation. At the last, a number of interstitial cystitis/bladder pain syndrome–regulating genes were found differentially expressed among different urothelial cell subpopulations. Conclusions Our study provides a comprehensive characterization of bladder urothelial cells, which is fundamental to understanding the biology of bladder urothelium and associated bladder disease.