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

View ORCID ProfileRenaud Mevel, View ORCID ProfileIvana Steiner, View ORCID ProfileSusan Mason, Laura C.A. Galbraith, View ORCID ProfileRahima Patel, View ORCID ProfileMuhammad ZH Fadlullah, Imran Ahmad, View ORCID ProfileHing Y. Leung, Pedro Oliveira, View ORCID ProfileKaren Blyth, View ORCID ProfileEsther Baena, View ORCID ProfileGeorges Lacaud
doi: https://doi.org/10.1101/2020.06.19.161604
Renaud Mevel
1Cancer Research UK, Stem Cell Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Alderley Edge, Macclesfield, SK10 4TG, UK.
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Ivana Steiner
2Cancer Research UK, Prostate Oncobiology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Alderley Edge, Macclesfield, SK10 4TG, UK.
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Susan Mason
3Cancer Research UK Beatson Institute, Bearsden, Glasgow, G61 1BD, UK.
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Laura C.A. Galbraith
3Cancer Research UK Beatson Institute, Bearsden, Glasgow, G61 1BD, UK.
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Rahima Patel
1Cancer Research UK, Stem Cell Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Alderley Edge, Macclesfield, SK10 4TG, UK.
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Muhammad ZH Fadlullah
1Cancer Research UK, Stem Cell Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Alderley Edge, Macclesfield, SK10 4TG, UK.
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Imran Ahmad
3Cancer Research UK Beatson Institute, Bearsden, Glasgow, G61 1BD, UK.
4Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Bearsden, Glasgow, G61 1QH, UK.
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Hing Y. Leung
3Cancer Research UK Beatson Institute, Bearsden, Glasgow, G61 1BD, UK.
4Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Bearsden, Glasgow, G61 1QH, UK.
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Pedro Oliveira
5Department of Pathology, The Christie NHS Foundation Trust, Manchester, UK.
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Karen Blyth
3Cancer Research UK Beatson Institute, Bearsden, Glasgow, G61 1BD, UK.
4Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Bearsden, Glasgow, G61 1QH, UK.
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Esther Baena
2Cancer Research UK, Prostate Oncobiology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Alderley Edge, Macclesfield, SK10 4TG, UK.
6Belfast-Manchester Movember Centre of Excellence, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park SK10 4TG, UK.
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Georges Lacaud
1Cancer Research UK, Stem Cell Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Alderley Edge, Macclesfield, SK10 4TG, UK.
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  • For correspondence: georges.lacaud@manchester.ac.uk
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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.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • http://shiny.cruk.manchester.ac.uk/pscapp/

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 28, 2020.
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RUNX1 marks a luminal castration resistant lineage established at the onset of prostate development
Renaud Mevel, Ivana Steiner, Susan Mason, Laura C.A. Galbraith, Rahima Patel, Muhammad ZH Fadlullah, Imran Ahmad, Hing Y. Leung, Pedro Oliveira, Karen Blyth, Esther Baena, Georges Lacaud
bioRxiv 2020.06.19.161604; doi: https://doi.org/10.1101/2020.06.19.161604
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RUNX1 marks a luminal castration resistant lineage established at the onset of prostate development
Renaud Mevel, Ivana Steiner, Susan Mason, Laura C.A. Galbraith, Rahima Patel, Muhammad ZH Fadlullah, Imran Ahmad, Hing Y. Leung, Pedro Oliveira, Karen Blyth, Esther Baena, Georges Lacaud
bioRxiv 2020.06.19.161604; doi: https://doi.org/10.1101/2020.06.19.161604

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