PhD Student The University of Texas at Dallas, United States
Umar Patel1; Hsin-Jung Tien1; Prashant Nuthalapati1; Purna A. Joshi1
1. Department of Biological Sciences, The University of Texas at Dallas, Richardson, Texas, United States
The oviduct comprises epithelial cell types and a stromal microenvironment that together facilitate oviduct function, including gamete transport, fertilization and early embryonic development. Although it is known that the oviductal epithelium experiences significant damage during ovulatory cycles, key progenitor cells involved in post-ovulatory oviductal regeneration are largely unknown. Defining progenitors and underlying mechanisms involved in oviductal regeneration and homeostasis are pivotal for understanding and addressing infertility and malignancy. In particular, progenitors in the stroma that may participate in oviductal regeneration remain tenuous and underexplored. In the uterus and mammary gland, mesenchymal cells expressing Platelet-Derived Growth Factor Receptor alpha (PDGFRα) are reported to contribute to epithelial lineages during regeneration. The objective of our study is to characterize PDGFRα+ cells in the oviduct and determine their fate and function in oviductal regeneration. Through immunofluorescence and flow cytometry studies on isolated oviducts from female Pdgfrα reporter mice, and analysis of published single-cell RNA sequencing datasets, we have observed that PDGFRα expression is restricted to mesenchymal cells in the oviductal stromal microenvironment, and absent from epithelial cells including secretory and ciliated cells. PDGFRα+ oviduct cells also express sex hormone receptors as detected by immunofluorescence and analysis of single-cell RNA sequencing data, suggesting that these stromal cells are likely hormone-responsive. Further, we found that Pdgfrα-expressing oviductal stromal cells fluctuate during the hormone-driven estrous cycle, exhibiting an increase in the post-ovulatory phase. Notably, the Pdgfrα-expressing stromal fraction purified by fluorescenceactivated cell sorting had significantly more clonogenic capacity compared to Pdgfrα-negative stromal cells, indicating that the Pdgfrα-expressing population enriches for stromal progenitors in the oviduct. These findings illuminate a hormone-responsive stromal progenitor in the murine oviduct and our ongoing work is addressing the functional contribution of these progenitors to oviductal regeneration. We envision that this work will lay a foundation for the development of novel cell-targeted therapeutics for oviductal regenerative medicine and cancer.
