Details

Autor(en) / Beteiligte

• Raths, Florian
• Karimzadeh, Mehran
• Ing, Nathan
• Martinez, Andrew
• Yang, Yoona
• Qu, Ying
• Lee, Tian-Yu
• Mulligan, Brianna
• Devkota, Suzanne
• Tilley, Wayne T.
• Hickey, Theresa E.
• Wang, Bo
• Giuliano, Armando E.
• Bose, Shikha
• Goodarzi, Hani
• Ray, Edward C.
• Cui, Xiaojiang
• Knott, Simon R.V.

Titel

The molecular consequences of androgen activity in the human breast

Ist Teil von

• Cell genomics, 2023-03, Vol.3 (3), p.100272-100272, Article 100272

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• Estrogen 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. [Display omitted] •A multi-omic atlas of breast tissues from individuals treated with androgen therapy•Hormone receptor-expressing (HR+) cells undergo gender-biased reprogramming•Paracrine signaling relays androgen effects from HR+ cells to other cell types•Androgen shapes breast morphology, immune composition, and metabolism Raths et al. analyzed breast tissue from individuals receiving gender-affirming androgen therapy. Androgen shrunk ductal structures, induced gender-biased transcriptional changes, and reshaped the stromal compartment of the breast. Changes were induced directly through the androgen receptor or indirectly through paracrine signaling to cells lacking hormone receptors.