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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>While the mesonephros persists in the adult mouse ovary and contributes to folliculogenesis, its inductive role in oogonial stem cell (OSC) differentiation remains uncertain. In this study, we investigated whether mesonephros-derived cells direct OSCs toward follicle-like structures in vitro. OSCs were co-cultured with mesonephros cells, and morphological assessments and factor expression analyses were conducted at multiple time points. On day 14 of co-culture, 10\u00d7 Genomics single-cell and bulk RNA sequencing were performed to profile transcriptomic changes, while renal capsule transplantation was conducted to evaluate the functional potential of co-cultured clusters in recipient mice. Transcriptomic analyses revealed a robust expression of mesonephros-specific genes and a significant enrichment of PI3K\/AKT pathway-associated genes in co-cultured cells. Notably, transplanted clusters exhibited signs of estrogen secretion with maintained graft integrity. Collectively, these findings demonstrate that the mesonephros promotes OSC differentiation into follicle-like structures, with the PI3K\/AKT pathway identified as a candidate mediator of this process. Our study provides novel insights into the developmental regulation of ovarian folliculogenesis and offers a valuable experimental model for future investigations.<\/jats:p>","DOI":"10.3390\/ijms27198719","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:14:37Z","timestamp":1790694877000},"page":"8719","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mouse Mesonephros Promotes Differentiation of Oogonial Stem Cells into Follicle-like Structures via the PI3K\/AKT Signaling Pathway"],"prefix":"10.3390","volume":"27","author":[{"given":"Jie","family":"Chen","sequence":"first","affiliation":[{"name":"College of Basic Medicine, Inner Mongolia Medical University, Hohhot 010000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Ziyao","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Inner Mongolia Medical University, Hohhot 010000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Rui","family":"Xiao","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Inner Mongolia Medical University, Hohhot 010000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Shaojie","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Inner Mongolia Medical University, Hohhot 010000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Yunteng","family":"Hao","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Inner Mongolia Medical University, Hohhot 010000, China"},{"name":"Digital Medical Center, Inner Mongolia Medical University, Hohhot 010000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"}]},{"given":"Xing","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Inner Mongolia Medical University, Hohhot 010000, China"},{"name":"Digital Medical Center, Inner Mongolia Medical University, Hohhot 010000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/nature02316","article-title":"Germline stem cells and follicular renewal in the postnatal mammalian ovary","volume":"428","author":"Johnson","year":"2004","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/ncb1869","article-title":"Production of offspring from a germline stem cell line derived from neonatal ovaries","volume":"11","author":"Zou","year":"2009","journal-title":"Nat. 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