RUNX1 marks a luminal castration resistant lineage established at the onset of prostate development
- Cancer Research UK Manchester Institute, The University of Manchester, United Kingdom
- Cancer Research UK Beatson Institute, United Kingdom
- The Christie NHS Foundation Trust, United Kingdom
Abstract
The characterization of prostate epithelial hierarchy and lineage heterogeneity is critical to understand its regenerative properties and malignancies. Here, we report that the transcription factor RUNX1 marks a specific subpopulation of proximal luminal cells (PLCs), enriched in the periurethral region of the developing and adult mouse prostate, and distinct from the previously identified NKX3.1+ luminal castration resistant cells. Using scRNA-seq profiling and genetic lineage tracing, we show that RUNX1+ PLCs are unaffected by androgen deprivation, and do not contribute to the regeneration of the distal luminal compartments. Furthermore, we demonstrate that a transcriptionally similar RUNX1+ population emerges at the onset of embryonic prostate specification to populate the proximal region of the ducts. Collectively, our results reveal that RUNX1+ PLCs is an intrinsic castration-resistant and self-sustained lineage that emerges early during prostate development and provide new insights into the lineage relationships of the prostate epithelium.
Data availability
Raw sequencing files and processed gene expression matrices have been deposited in the NCBI Gene Expression Omnibus under the accession number GSE151944. The processed datasets for both mouse adult prostate and UGS prostate explant cultures can be accessed via a searchable R Shiny application available at http://shiny.cruk.manchester.ac.uk/pscapp/. All code used to process data and generate figures is available on a public GitHub repository at https://github.com/glacaud/prostate-scRNAseq.
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Runx1 marks a luminal castration resistant lineage established at the onset of prostate developmentNCBI Gene Expression Omnibus, GSE151944.
Article and author information
Author details
Funding
Cancer Research UK (C5759/A20971)
- Esther Baena
- Georges Lacaud
Cancer Research UK (C596/A17196)
- Karen Blyth
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Wilbert Zwart, Netherlands Cancer Institute, Netherlands
Ethics
Animal experimentation: Animal experiments were approved by the Animal Welfare and Ethics Review Body (AWERB) of the Cancer Research UK Manchester Institute and conducted according to the UK Home Office Project Licence (PPL 70/8580). Genetic lineage-tracing experiments were performed at the Beatson Biological Services Unit (PPL 70/8645 & P5EE22AEE) and approved by the University of Glasgow AWERB. Mice were maintained in purpose-built facility in a 12-hour light/dark cycle with continual access to food and water. All animal procedures were performed on adult males at least 7 weeks of age. Surgical castration was carried out under aseptic conditions.
Version history
- Received: June 20, 2020
- Accepted: October 6, 2020
- Accepted Manuscript published: October 7, 2020 (version 1)
- Version of Record published: November 5, 2020 (version 2)
Copyright
© 2020, Mevel et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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RUNX1 marks a luminal castration resistant lineage established at the onset of prostate development
eLife 9:e60225.
https://doi.org/10.7554/eLife.60225
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