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The molecular consequences of androgen activity in the human breast

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dc.contributor.authorRaths, F.
dc.contributor.authorKarimzadeh, M.
dc.contributor.authorIng, N.
dc.contributor.authorMartinez, A.
dc.contributor.authorYang, Y.
dc.contributor.authorQu, Y.
dc.contributor.authorLee, T.-Y.
dc.contributor.authorMulligan, B.
dc.contributor.authorDevkota, S.
dc.contributor.authorTilley, W.T.
dc.contributor.authorHickey, T.E.
dc.contributor.authorWang, B.
dc.contributor.authorGiuliano, A.E.
dc.contributor.authorBose, S.
dc.contributor.authorGoodarzi, H.
dc.contributor.authorRay, E.C.
dc.contributor.authorCui, X.
dc.contributor.authorKnott, S.R.V.
dc.date.issued2023
dc.descriptionPublished: March 8, 2023
dc.description.abstractEstrogen and progesterone have been extensively studied in the mammary gland, but the molecular effects of androgen remain largely unexplored. Transgender men are recorded as female at birth but identify as male and may undergo gender-affirming androgen therapy to align their physical characteristics and gender identity. Here we perform single-cell-resolution transcriptome, chromatin, and spatial profiling of breast tissues from transgender men following androgen therapy. We find canonical androgen receptor gene targets are upregulated in cells expressing the androgen receptor and that paracrine signaling likely drives sex-relevant androgenic effects in other cell types. We also observe involution of the epithelium and a spatial reconfiguration of immune, fibroblast, and vascular cells, and identify a gene regulatory network associated with androgen-induced fat loss. This work elucidates the molecular consequences of androgen activity in the human breast at single-cell resolution.
dc.description.statementofresponsibilityFlorian Raths, Mehran Karimzadeh, Nathan Ing, Andrew Martinez, Yoona Yang, Ying Qu, Tian-Yu Lee, Brianna Mulligan, Suzanne Devkota, Wayne T. Tilley, Theresa E. Hickey, Bo Wang, Armando E. Giuliano, Shikha Bose, Hani Goodarzi, Edward C. Ray, Xiaojiang Cui, and Simon R.V. Knott
dc.identifier.citationCell Genomics, 2023; 3(3):100272-1-100272-29
dc.identifier.doi10.1016/j.xgen.2023.100272
dc.identifier.issn2666-979X
dc.identifier.issn2666-979X
dc.identifier.orcidTilley, W.T. [0000-0003-1893-2626]
dc.identifier.orcidHickey, T.E. [0000-0002-2752-730X]
dc.identifier.urihttps://hdl.handle.net/2440/141477
dc.language.isoen
dc.publisherCell Press (Elsevier)
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1084416
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1130077
dc.rights© 2023 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
dc.source.urihttps://doi.org/10.1016/j.xgen.2023.100272
dc.subjectandrogen regulation of human breast homeostasis
dc.subjectbreast microenvironment
dc.subjectcellular metabolism
dc.subjectchromatin regulation
dc.subjecthormone receptor
dc.subjectlactation
dc.subjectmultiplexed immunohistochemistry by co-detection by indexing
dc.subjectsingle-cell ATAC sequencing
dc.subjectsingle-cell RNA sequencing
dc.subjecttranscriptional control
dc.titleThe molecular consequences of androgen activity in the human breast
dc.typeJournal article
pubs.publication-statusPublished

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