A single-cell atlas of the mouse and human prostate reveals heterogeneity and conservation of epithelial progenitors.

Weiping Li,Massimo Loda,Hanina Hibshoosh,Shouhong Xuan,Michael M Shen,Laura Crowley,Luis Aparicio,Maho Shibata,Raul Rabadan,Brian D Robinson,Francesco Cambuli

doi:10.7554/elife.59465

Weiping Li, Massimo Loda + Show 9 more

Open Access

https://doi.org/10.7554/elife.59465

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Abstract

Understanding the cellular constituents of the prostate is essential for identifying the cell of origin for prostate adenocarcinoma. Here, we describe a comprehensive single-cell atlas of the adult mouse prostate epithelium, which displays extensive heterogeneity. We observe distal lobe-specific luminal epithelial populations (LumA, LumD, LumL, and LumV), a proximally enriched luminal population (LumP) that is not lobe-specific, and a periurethral population (PrU) that shares both basal and luminal features. Functional analyses suggest that LumP and PrU cells have multipotent progenitor activity in organoid formation and tissue reconstitution assays. Furthermore, we show that mouse distal and proximal luminal cells are most similar to human acinar and ductal populations, that a PrU-like population is conserved between species, and that the mouse lateral prostate is most similar to the human peripheral zone. Our findings elucidate new prostate epithelial progenitors, and help resolve long-standing questions about anatomical relationships between the mouse and human prostate.

Highlights

Significant anatomical differences between the mouse and human prostate have long hindered analyses of mouse models of prostate diseases
We noted that the anterior (AP), dorsal (DP), and lateral (LP) lobes joined the urethra in close proximity on the dorsal side, whereas the ventral lobe (VP) had a distinct junction ventrally
To examine the lobe-specificity and spatial distribution of these luminal populations, we identified candidate markers based on gene expression patterns in our single-cell datasets

Summary

Introduction

Significant anatomical differences between the mouse and human prostate have long hindered analyses of mouse models of prostate diseases. The mouse prostate can be separated into anterior (AP), dorsal (DP), lateral (LP), and ventral (VP) lobes; the mouse dorsal and lateral lobes are often combined as the dorsolateral prostate (DLP) (Cunha et al, 1987; Shappell et al, 2004; Shen and Abate-Shen, 2010). The human prostate lacks defined lobes, and instead is divided into different histological zones (central, transition, and peripheral); the peripheral zone represents the predominant site of prostate adenocarcinoma, whereas benign prostatic hyperplasia (BPH) occurs in the transition zone (Cunha et al, 2018; Ittmann, 2018; Shappell et al, 2004).

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