Evidence map›Paper›PMID 40854129›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

Cellular cartography reveals mouse prostate organization and determinants of castration resistance.

Hanbyul Cho, Yuping Zhang, Jean C Tien, Rahul Mannan, Jie Luo, Sathiya Pandi Narayanan, Somnath Mahapatra, Jing Hu, Greg Shelley, Gabriel Cruz and 9 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Cellular cartography reveals mouse prostate organization and determinants of castration resistance.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Hanbyul Cho *Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109.
Yuping Zhang *Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109.ORCID 0000-0002-8727-5183
Jean C TienMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109.ORCID 0000-0002-2684-4450
Rahul MannanMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109.ORCID 0000-0002-6642-0468
Jie LuoMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109.ORCID 0009-0009-7307-7133
Sathiya Pandi NarayananMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109.
Somnath MahapatraMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109.
Jing HuMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109.
Greg ShelleyDepartment of Urology, University of Michigan, Ann Arbor, MI 48109.
Gabriel CruzMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109.
Miriam ShahineMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109.
Lisha WangMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109.
Fengyun SuMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109.
Rui WangMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109.ORCID 0000-0002-5356-9685
Xuhong CaoMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109.
Saravana Mohan DhanasekaranMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109.
Evan T Keller *Department of Pathology, University of Michigan, Ann Arbor, MI 48109.ORCID 0000-0002-7592-7535
Sethuramasundaram Pitchiaya *Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109.ORCID 0000-0003-2529-5186
Arul M Chinnaiyan *Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109.ORCID 0000-0001-9282-3415

Funding

Tissue/InformaticsP50CA186786 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Ganesh S Palapattu · 2014 to 2026
$27.6M
Exploring Precision Oncology: From Gene Fusions to lncRNAsR35CA231996 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHINNAIYAN, ARUL M · 2018 to 2024
$6.4M
Michigan-VUMC Biomarker Characterization CenterU2CCA271854 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jeffrey John Tosoian · 2022 to 2026
$5.4M
DOD | MHS | CDMRP | DOD Prostate Cancer Research Program (PCRP) W81XWH1910424HHS | NIH | National Cancer Institute (NCI) P010939000HHS | NIH | National Cancer Institute (NCI) P50CA186786HHS | NIH | National Cancer Institute (NCI) R35CA231996HHS | NIH | National Cancer Institute (NCI) U2C-CA271854NCI NIH HHS P50 CA186786NCI NIH HHS R35 CA231996NCI NIH HHS U2C CA271854Prostate Cancer Foundation (PCF) 18YOUN20
6 · The paper itself

Abstract

Inadequate response to androgen deprivation therapy (ADT) frequently arises in prostate cancer, driven by cellular mechanisms that remain poorly understood. Here, we integrated single-cell RNA sequencing, single-cell multiomics, and spatial transcriptomics to define the transcriptional, epigenetic, and spatial basis of cell identity and castration response in the mouse prostate. Leveraging these data along with a meta-analysis of human prostates and prostate cancer (PCa), we identified cellular orthologs and key determinants of ADT response and resistance. Our findings reveal that mouse prostates harbor lobe-specific luminal epithelial cell types distinguished by unique gene regulatory modules and anatomically defined androgen-responsive transcriptional programs, indicative of divergent developmental origins. Androgen-insensitive, stem-like epithelial populations-resembling human club and hillock cells-are notably enriched in the urethra and ventral prostate but are rare in other lobes. Within the ventral prostate, we also uncovered two additional androgen-responsive luminal epithelial cell types, marked by Pbsn or Spink1 expression, which align with human luminal subsets and may define the origin of distinct PCa subtypes. Castration profoundly reshaped luminal epithelial transcriptomes, with castration-resistant luminal epithelial cells activating stress-responsive and stemness programs. These transcriptional signatures are enriched in tumor cells from ADT-treated and castration-resistant PCa patients, underscoring their likely role in driving treatment resistance. Temporal tracking of cells will precisely map disease-associated cellular transitions, and our technical framework facilitates such interrogations. Collectively, our comprehensive cellular atlas of the mouse prostate illuminates the importance of lobe-specific contexts for PCa modeling and reveals potential therapeutic targets to counter castration resistance.

Indexed as

ProstateProstatic Neoplasms, Castration-ResistantAndrogen AntagonistsAndrogensAnimalsEpithelial CellsGene Expression Regulation, NeoplasticHumansMaleMiceProstatic NeoplasmsSingle-Cell AnalysisTranscriptomeAndrogen AntagonistsAndrogensandrogen signallingcastration resistant prostate cancersingle-cell multiomicssingle-cell RNA sequencingspatial transcriptomics

Identifiers

PMID40854129
PMCPMC12415206

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.