RUNX1 marks a luminal castration-resistant lineage established at the onset of prostate development

Mevel, R. et al. (2020) RUNX1 marks a luminal castration-resistant lineage established at the onset of prostate development. eLife, 9, e60225. (doi: 10.7554/elife.60225) (PMID:33025905) (PMCID:PMC7644213)

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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.

Item Type:Articles
Additional Information:Funding: Cancer Research UK C5759/A20971 and C596/A17196.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ahmad, Dr Imran and Mason, Miss Susan and Blyth, Professor Karen and Leung, Professor Hing and Galbraith, Dr Laura
Creator Roles:
Mason, S.Investigation
Galbraith, L. C.A.Investigation
Ahmad, I.Resources
Leung, H. Y.Resources
Blyth, K.Conceptualization, Supervision, Funding acquisition, Methodology, Writing – review and editing
Authors: Mevel, R., Steiner, I., Mason, S., Galbraith, L. C.A., Patel, R., Fadlullah, M. Z.H., Ahmad, I., Leung, H. Y., Oliveira, P., Blyth, K., Baena, E., and Lacaud, G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:eLife
Publisher:eLife Sciences Publications
ISSN:2050-084X
ISSN (Online):2050-084X
Copyright Holders:Copyright © 2020 Mevel et al.
First Published:First published in eLife 9: e60225
Publisher Policy:Reproduced under a Creative Commons License

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