1. Androgen action in cell fate and communication during prostate development at single-cell resolution.
- Author
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Dong-Hoon Lee, Olson, Adam W., Jinhui Wang, Won Kyung Kim, Jiaqi Mi, Hong Zeng, Vien Le, Aldahl, Joseph, Alex Hiroto, Xiwei Wu, and Zijie Sun
- Subjects
CELL communication ,PROSTATE ,ANDROGENS ,ANDROGEN receptors ,EMBRYOLOGY ,CELL populations - Abstract
Androgens/androgen receptor (AR)-mediated signaling pathways are essential for prostate development, morphogenesis and regeneration. Specifically, stromal AR signaling has been shown to be essential for prostatic initiation. However, the molecular mechanisms underlying AR-initiated mesenchymal-epithelial interactions in prostate development remain unclear. Here, using a newly generated mouse model,we have directlyaddressed the fate and role of genetically marked AR-expressing cells during embryonic prostate development. Androgen signaling-initiated signaling pathways were identified in mesenchymal niche populations at single-cell transcriptomic resolution. The dynamic cell-signaling networks regulated by stromal AR were additionally characterized in relation to prostatic epithelial bud formation. Pseudotime analyses further revealed the differentiation trajectory and fate of AR-expressing cells in both prostatic mesenchymal and epithelial cell populations. Specifically, the cellular properties of Zeb1-expressing progenitors were assessed. Selective deletion of AR signaling in a subpopulation of mesenchymal rather than epithelial cells dysregulated the expression of the master regulators and significantly impaired prostatic bud formation. These data provide novel, high-resolution evidence demonstrating the important role of mesenchymal androgen signaling in the cellular niche controlling prostate early development by initiating dynamic mesenchyme-epithelia cell interactions. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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