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 |
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Additional Information: | Funding: Cancer Research UK C5759/A20971 and C596/A17196. |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Ahmad, Professor Imran and Blyth, Professor Karen and Leung, Professor Hing and Mason, Miss Susan 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 > School 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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