Abstract
The basal cell compartment in many epithelial tissues is generally believed to serve as an important pool of stem cells. However, basal cells are heterogenous and the stem cell subpopulation within basal cells is not well elucidated. Here we uncover that the core epithelial-to-mesenchymal transition (EMT) inducer Zeb1 is expressed in a prostate basal cell subpopulation. The Zeb1+ prostate epithelial cells are multipotent prostate basal stem cells (PBSCs) that can self-renew and generate functional prostatic glandular structures at the single-cell level. Genetic ablation studies reveal an indispensable role for Zeb1 in prostate basal cell development. Utilizing unbiased single-cell transcriptomic analysis of over 9000 mouse prostate basal cells, we confirm the existence of the Zeb1+ basal cell subset. Moreover, Zeb1+ epithelial cells can be detected in mouse and human prostate tumors. Identification of the PBSC and its transcriptome profile is crucial to advance our understanding of prostate development and tumorigenesis.
Highlights
The basal cell compartment in many epithelial tissues is generally believed to serve as an important pool of stem cells
Expression and function of core transcriptional factors such as Zeb1/2, Snai1/2, Twist1/2 which are required for epithelialto-mesenchymal transition (EMT) induction, have not been examined in normal prostate epithelia under physiological condition
We asked whether core EMT inducers are present in normal prostate basal cells
Summary
The basal cell compartment in many epithelial tissues is generally believed to serve as an important pool of stem cells. Using the K14rtTA/TetOCRE/RosaYFP or K5CREER/ RosaYFP pan-basal cell lineage tracing mice, it has been shown that multipotent basal stem cells can contribute to the differentiation of prostate basal, luminal and neuroendocrine cell lineages especially during early postnatal development[13]. From a study of quantitative clonal mapping and three-dimensional reconstruction of adult human prostates, Moad et al recently reported that multipotent basal stem cells are exclusively located in juxta-urethral niches and function in a directed migratory way to generate epithelial progenitors[24]. We identify a PBSC subpopulation that expresses Zeb[1], an important EMT inducer[30,31], through both in vitro and in vivo functional, lineage tracing and genetic ablation analyses. Our single-cell transcriptomics data provide additional supporting evidence for the existence of Zeb1-expressing PBSCs and uncover their gene expression profile
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