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Human prostate organoid generation and the identification of prostate development drivers using inductive rodent tissues

Lookup NU author(s): Parmveer Singh, Hannah Kendall, Laura WilsonORCiD, Ryan Long, Dr Adriana BuskinORCiD, Dr Colin Miles, Professor Rakesh Heer, Professor Craig Robson

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Abstract

© 2023. Published by The Company of Biologists Ltd. The reactivation of developmental genes and pathways during adulthood may contribute to pathogenesis of diseases such as prostate cancer. Analysis of the mechanistic links between development and disease could be exploited to identify signalling pathways leading to disease in the prostate. However, the mechanisms underpinning prostate development require further characterisation to interrogate fully the link between development and disease. Previously, our group developed methods to produce prostate organoids using induced pluripotent stem cells (iPSCs). Here, we show that human iPSCs can be differentiated into prostate organoids using neonatal rat seminal vesicle mesenchyme in vitro. The organoids can be used to study prostate development or modified to study prostate cancer. We also elucidated molecular drivers of prostate induction through RNA-sequencing analyses of the rat urogenital sinus and neonatal seminal vesicles. We identified candidate drivers of prostate development evident in the inductive mesenchyme and epithelium involved with prostate specification. Our top candidates included Spx, Trib3, Snai1, Snai2, Nrg2 and Lrp4. This work lays the foundations for further interrogation of the reactivation of developmental genes in adulthood, leading to prostate disease.


Publication metadata

Author(s): Singh P, Lanman NA, Kendall HLR, Wilson L, Long R, Franco OE, Buskin A, Miles CG, Hayward SW, Heer R, Robson CN

Publication type: Article

Publication status: Published

Journal: Development

Year: 2023

Volume: 150

Issue: 13

Online publication date: 12/07/2023

Acceptance date: 20/06/2023

ISSN (print): 0950-1991

ISSN (electronic): 1477-9129

Publisher: The Company of Biologists Ltd

URL: https://doi.org/10.1242/dev.201328

DOI: 10.1242/dev.201328

PubMed id: 37376888


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