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Lookup NU author(s): Matthew TeasdaleORCiD, Lewis Walker Walker, Laura WilsonORCiD, Rachel Howarth, Dr Sara Saleem, Jamie Logsdon, Dr Anastasia Hepburn, Ryan Nelson, Dr Andrey Elizondo Solano, Raf Hussain, Dr Jonathan Coxhead, Dr Luke GaughanORCiD, Professor Majlinda LakoORCiD, Emma Scott, Professor Craig RobsonORCiD, Professor Rakesh Heer, Dr Adriana Buskin
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2026 The AuthorsCurrent prostate organoid models rely on tissue-derived material or animal components and lack epithelial and stromal complexity. We defined a xeno-free system to generate human prostate organoids from induced pluripotent stem cells with consistent multilineage differentiation. Organoids formed as free-floating 3D aggregates self-organized into the epithelial and stromal domains with basal, luminal, neuroendocrine, fibroblast, and smooth muscle markers. In an alternative modular co-culture system, engineered epithelial progenitors aggregated with wild-type mesenchymal progenitors, enabling compartment-specific manipulation. Androgen receptor (AR)-overexpressing organoids showed increased epithelial AR and prostate-specific antigen (PSA) expression and proliferation. Single-cell transcriptomics, together with qPCR and immunostaining, confirmed prostate lineage specification and tissue organization. This xeno-free platform provides a reproducible, scalable, and genetically tractable model to study in vitro prostate lineage programs, epithelial and stromal interactions, and disease biology.
Author(s): Shaikh N, Teasdale M, Walker LJ, Wilson L, Howarth R, Saleem S, Logsdon J, Hepburn AC, Nelson R, Lian Q, Elizondo AC, Hussain R, Coxhead J, Gaughan L, Lako M, Scott E, Robson CN, Simons B, Hayward SW, Strand DW, Heer R, Buskin A
Publication type: Article
Publication status: Published
Journal: Cell Reports Methods
Year: 2026
Online publication date: 29/07/2026
Acceptance date: 01/07/2026
Date deposited: 18/08/2026
ISSN (electronic): 2667-2375
Publisher: Cell Press
URL: https://doi.org/10.1016/j.crmeth.2026.101538
DOI: 10.1016/j.crmeth.2026.101538
Data Access Statement: Bulk and single-cell RNA sequencing datasets generated during this study can be found at the following link: https://doi.org/10.5281/zenodo.20427357. This paper does not report original code. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.
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