The Human Male Mammary Gland has Similar Epithelial Populations to Female but Distinct Composition and Transcriptional Properties

mRNA, enrichment of RNA processing and ribosome biogenesis programs, reduced inflammatory cytokine and growth factor signaling, elevated estradiol gene set enrichment scores, and higher inferred activity of developmental patterning transcription factors. This pattern was observed across differential expression, gene ontology, ligand profiling, and regulon-based analyses, and was not restricted to sex chromosome-linked gene expression. This is consistent with the near-universal estrogen receptor (ER) positivity that characterizes MBC clinically. This atlas provides the first cellular and transcriptional reference for the normal male breast and a resource for investigating sex differences in mammary biology, germline susceptibility variant interpretation, and modeling breast malignancies.

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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-03-31
DOI
https://doi.org/10.64898/2026.03.27.714915
Primary Topic
Male Breast Health Studies
Type
article
Field-Weighted Citation Impact
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article

The Human Male Mammary Gland has Similar Epithelial Populations to Female but Distinct Composition and Transcriptional Properties

Nagarajan Kannan, Chitra Priya Emperumal, Mark E. Sherman, Syed Mohammed Musheer Aalam et al.
bioRxiv (Cold Spring Harbor Laboratory)
Male Breast Health Studies
article

The Human Male Mammary Gland has Similar Epithelial Populations to Female but Distinct Composition and Transcriptional Properties

Nagarajan Kannan, Chitra Priya Emperumal, Mark E. Sherman, Syed Mohammed Musheer Aalam, Sarah A. McLaughlin, David J.H.F. Knapp, Anguraj Sadanandam, M. Iliana Ibañez-Rios, Siddhartha Yadav, Megan L. Ritting, James W Jakub, Derek Radisky, Amy C Degnim, Ashlyn Jore
article en

Abstract

mRNA, enrichment of RNA processing and ribosome biogenesis programs, reduced inflammatory cytokine and growth factor signaling, elevated estradiol gene set enrichment scores, and higher inferred activity of developmental patterning transcription factors. This pattern was observed across differential expression, gene ontology, ligand profiling, and regulon-based analyses, and was not restricted to sex chromosome-linked gene expression. This is consistent with the near-universal estrogen receptor (ER) positivity that characterizes MBC clinically. This atlas provides the first cellular and transcriptional reference for the normal male breast and a resource for investigating sex differences in mammary biology, germline susceptibility variant interpretation, and modeling breast malignancies.

bioRxiv (Cold Spring Harbor Laboratory)
Mayo Clinic (US), Institute of Cancer Research (GB), Oklahoma City University (US), Breast Cancer Now (GB), Cancer Research UK (GB), Institute for Research in Immunology and Cancer (CA), Mayo Clinic in Arizona (US), Mayo Clinic in Florida (US), University of Oklahoma (US)
Good health and well-being
Openalex Percentile: Top 31%
Male Breast Health Studies
DOIOpen Access PDFOpenAlex
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