Single‐cell transcriptomes of mouse bladder urothelium uncover novel cell type markers and urothelial differentiation characteristics

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‐...

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Bibliographic Details
Published in:Cell proliferation 2021-04, Vol.54 (4), p.e13007-n/a
Main Authors: Li, Yan, Liu, Yaxiao, Gao, Zhengdong, Zhang, Lekai, Chen, Lipeng, Wu, Zonglong, Liu, Qinggang, Wang, Shuai, Zhou, Nan, Chai, Toby C., Shi, Benkang
Format: Article
Language:English
Subjects:
Animals
Biomarkers
Biomarkers - metabolism
Bladder
Bladder cancer
bladder urothelium
Calmodulin-Binding Proteins - genetics
Calmodulin-Binding Proteins - metabolism
Cell Differentiation
Cell Lineage
cell subtype
Cells
Cells (biology)
Cluster analysis
Clustering
Cystitis
Differentiation (biology)
Disease Models, Animal
Enzymes
Female
Gene expression
Gene sequencing
Genes
Genomics
Immunofluorescence
Laboratory animals
Mice
Mice, Inbred C57BL
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Original
Pain
Principal components analysis
Progenitor cells
Receptors, Cell Surface - genetics
Receptors, Cell Surface - metabolism
Ribonucleic acid
RNA
Sequence Analysis, RNA
Single-Cell Analysis
single‐cell transcriptome
Stem cells
Stem Cells - cytology
Stem Cells - metabolism
Subpopulations
Transcription factors
Transcription Factors - genetics
Transcription Factors - metabolism
Transcriptome
Transcriptomes
Urinary Bladder - cytology
Urinary tract
Urinary Tract Infections - metabolism
Urinary Tract Infections - pathology
Urothelium
Urothelium - cytology
Urothelium - metabolism
Velocity
Wound healing
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Summary: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. 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. 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. 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 proge
ISSN:0960-7722
1365-2184
DOI:10.1111/cpr.13007