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ResearchIn-Press PreviewCell biologyReproductive biology Open Access | 10.1172/jci.insight.176479

Spatial transcriptomics identifies candidate stromal drivers of benign prostatic hyperplasia

Anna S. Pollack,1 Christian A. Kunder,1 Noah Brazer,1 Zhewei Shen,1 Sushama Varma,1 Robert B. West,1 Gerald R. Cunha,2 Laurence S. Baskin,2 James D. Brooks,3 and Jonathan R. Pollack4

1Department of Pathology, Stanford University, Stanford, United States of America

2Department of Pediatric Urology, University of California, San Francisco, United States of America

3Department of Urology, Stanford University, Stanford, United States of America

4Stanford University, Stanford, United States of America

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1Department of Pathology, Stanford University, Stanford, United States of America

2Department of Pediatric Urology, University of California, San Francisco, United States of America

3Department of Urology, Stanford University, Stanford, United States of America

4Stanford University, Stanford, United States of America

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1Department of Pathology, Stanford University, Stanford, United States of America

2Department of Pediatric Urology, University of California, San Francisco, United States of America

3Department of Urology, Stanford University, Stanford, United States of America

4Stanford University, Stanford, United States of America

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1Department of Pathology, Stanford University, Stanford, United States of America

2Department of Pediatric Urology, University of California, San Francisco, United States of America

3Department of Urology, Stanford University, Stanford, United States of America

4Stanford University, Stanford, United States of America

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1Department of Pathology, Stanford University, Stanford, United States of America

2Department of Pediatric Urology, University of California, San Francisco, United States of America

3Department of Urology, Stanford University, Stanford, United States of America

4Stanford University, Stanford, United States of America

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1Department of Pathology, Stanford University, Stanford, United States of America

2Department of Pediatric Urology, University of California, San Francisco, United States of America

3Department of Urology, Stanford University, Stanford, United States of America

4Stanford University, Stanford, United States of America

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1Department of Pathology, Stanford University, Stanford, United States of America

2Department of Pediatric Urology, University of California, San Francisco, United States of America

3Department of Urology, Stanford University, Stanford, United States of America

4Stanford University, Stanford, United States of America

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1Department of Pathology, Stanford University, Stanford, United States of America

2Department of Pediatric Urology, University of California, San Francisco, United States of America

3Department of Urology, Stanford University, Stanford, United States of America

4Stanford University, Stanford, United States of America

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1Department of Pathology, Stanford University, Stanford, United States of America

2Department of Pediatric Urology, University of California, San Francisco, United States of America

3Department of Urology, Stanford University, Stanford, United States of America

4Stanford University, Stanford, United States of America

Find articles by Brooks, J. in: JCI | PubMed | Google Scholar

1Department of Pathology, Stanford University, Stanford, United States of America

2Department of Pediatric Urology, University of California, San Francisco, United States of America

3Department of Urology, Stanford University, Stanford, United States of America

4Stanford University, Stanford, United States of America

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Published November 16, 2023 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.176479.
Copyright © 2023, Pollack et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published November 16, 2023 - Version history
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Abstract

Benign prostatic hyperplasia (BPH) is the nodular proliferation of the prostate transition zone in older men, leading to urinary storage and voiding problems that can be recalcitrant to therapy. Decades ago, John McNeal proposed that BPH originates with the “reawakening” of embryonic inductive activity by adult prostate stroma, which spurs new ductal proliferation and branching morphogenesis. Here, by laser microdissection and transcriptional profiling of the BPH stroma adjacent to hyperplastic branching ducts, we identified secreted factors likely mediating stromal induction of prostate glandular epithelium and coinciding processes. The top stromal factors were Insulin Like Growth Factor 1 (IGF1) and C-X-C Motif Chemokine Ligand 13 (CXCL13), which we confirmed by RNA in situ hybridization to be co-expressed in BPH fibroblasts, along with their cognate receptors (IGF1R and CXCR5) on adjacent epithelium. In contrast, IGF1 but not CXCL13 was expressed in human embryonic prostate stroma. Finally, we demonstrated that IGF1 is necessary for the generation of BPH-1 cell spheroids and patient-derived BPH cell organoids in three-dimensional culture. Our findings partially support historic speculations on the etiology of BPH, and provide what we believe to be new molecular targets for rational therapies directed against the underlying processes driving BPH.

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