Functional Heterogeneity of Mouse Prostate Stromal Cells Revealed by Single-Cell RNA-Seq

Oh-Joon Kwon; Yiqun Zhang; Yumei Li; Xing Wei; Li Zhang; Rui Chen; Chad J Creighton; Li Xin

doi:10.1016/j.isci.2019.02.032

Functional Heterogeneity of Mouse Prostate Stromal Cells Revealed by Single-Cell RNA-Seq

iScience. 2019 Mar 29:13:328-338. doi: 10.1016/j.isci.2019.02.032. Epub 2019 Mar 2.

Authors

Oh-Joon Kwon¹, Yiqun Zhang², Yumei Li³, Xing Wei⁴, Li Zhang⁵, Rui Chen³, Chad J Creighton⁶, Li Xin⁷

Affiliations

¹ Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA; Department of Urology, University of Washington, 850 Republican Street, Seattle, WA 98109, USA.
² Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
³ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
⁴ Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA; Graduate Program in Integrative Molecular and Biomedical Sciences, Baylor College of Medicine, Houston, TX, USA; Department of Urology, University of Washington, 850 Republican Street, Seattle, WA 98109, USA.
⁵ Department of Urology, University of Washington, 850 Republican Street, Seattle, WA 98109, USA.
⁶ Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA; Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
⁷ Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA; Department of Urology, University of Washington, 850 Republican Street, Seattle, WA 98109, USA; Institute of Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA. Electronic address: xin18@uw.edu.

Abstract

We perform a single-cell RNA sequencing analysis to investigate the phenotypic and functional heterogeneity of the adult mouse prostate stromal cells. Our analysis identifies three major cell populations representing the smooth muscle cells and two types of fibroblast cells enriched by Sca-1 and CD90. The Sca-1⁺CD90⁺ fibroblast cells are in direct contact with the epithelial cells and express growth factors and genes associated with cell motility, developmental process, and androgen biosynthesis. This suggests that they may regulate epithelial cell survival and growth. The Sca-1⁺CD90^-/low myofibroblast-like cells highly express genes associated with the extracellular matrix and cytokine-mediated signaling pathways, indicating a role in tissue repair and immune responses. The Sca-1⁺CD90^-/low cells significantly suppress the capacity of the basal cells for bipotent differentiation in the prostate organoid assay. Collectively, we identify the surface markers enabling physical separation of stromal subpopulations and generate the gene expression profiles implying their cellular functions.

Keywords: Biological Sciences; Cell Biology; Integrative Aspects of Cell Biology; Molecular Biology.

Abstract

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