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Updated: Jun 13, 2026
Cell-Specific Paired Interrogation of the Mouse Ovarian Epigenome and Transcriptome
Published on: February 24, 2023
Integrated single cell and spatial transcriptomics reveals the cellular and molecular mechanisms underlying UCMSCs
Chuan Tian1, Li Ye2, Xiangqing Zhu2
1Stem Cell Research Center, School of Medicine, Tongji University, Shanghai, 200311, China.
Background:
Ovarian aging reduces fertility and leads to endocrine disorders, umbilical cord mesenchymal stem cells (UCMSCs) therapy has clinical potential, but a deeper understanding of their cellular and molecular regulatory mechanisms is still required.
Methods:
The old female tree shrews were received UCMSCs treatment via tail vein injection, at 1 × 10⁷ cells/kg once daily for 3 days. Ovaries and peripheral blood were collected after UCMSCs therapy 3 months, HE staining was performed to observe the number of follicles, ELISA was used to detect the secretion of sex hormones, immunohistochemical and immunofluorescence staining was used to detect the expression of ovarian aging relative markers, and scRNA-seq and spatial transcriptomics were performed on ovaries to map the cellular spatial atlas, analyze aging-related scores, and reveal their cellular and molecular regulatory mechanisms.
Results:
UCMSCs increased the number of follicles, boosted the secretion of sex hormones, inhibited the expression of p16, and enhanced proliferation and autophagy in ovarian aging model of tree shrews, but did not fully recover to the level of the young group. Following UCMSCs therapy, the relative abundances of oocytes, theca cells, granulosa cells, perivascular cells, and epithelial cells increased, whereas those of stromal cells decreased, and intercellular communication between oocytes and granulosa, endothelial, and epithelial cells amplified. Within the follicle microenvironment, oocytes reduce genAge scores, and enhance DNA repair capacity. Granulosa cells reduce celluar senescence scores, downregulate CDKN1A, and increase proliferation. Theca cells exhibit enhance DNA repair. Stromal cells exhibit an expanded progenitor pool at the trajectory origin and significantly reduced geneAge and SASP scores. Mechanistically, ubiquitin B (UBB) is involved in positively regulating p53 family protein signaling and is positively correlated with SASP and genAge signatures, UCMSCs therapy significantly downregulated both UBB and p53 expression.
Conclusion:
UCMSCs therapy improves the structure and function of the aged ovary, regulates ovarian microenvironment, with UBB emerging as a potential therapeutic target.
Insights
Umbilical cord mesenchymal stem cells (UCMSCs) therapy improved aged ovarian function and structure in tree shrews. This treatment regulated the ovarian microenvironment, highlighting ubiquitin B (UBB) as a potential therapeutic target for ovarian aging.
Area of Science:
- Reproductive Biology
- Stem Cell Therapy
- Gerontology
Background:
- Ovarian aging diminishes fertility and causes endocrine disorders.
- Umbilical cord mesenchymal stem cells (UCMSCs) show therapeutic promise for ovarian aging.
- Understanding the cellular and molecular mechanisms of UCMSC therapy is crucial.
Purpose of the Study:
- To investigate the efficacy of UCMSC therapy in improving aged ovarian structure and function.
- To elucidate the cellular and molecular mechanisms underlying UCMSC-mediated ovarian rejuvenation.
- To identify potential therapeutic targets for ovarian aging.
Main Methods:
- UCMSC treatment administered to aged female tree shrews.
- Ovarian tissue and blood analysis including histology, ELISA, and molecular marker detection.
- Single-cell RNA sequencing and spatial transcriptomics to map ovarian cellular atlas and aging mechanisms.
Main Results:
- UCMSC therapy increased follicle count, sex hormone secretion, and ovarian cell abundance while reducing aging markers like p16 and UBB.
- Cellular analysis revealed enhanced DNA repair, proliferation, and autophagy, with reduced senescence and SASP scores in key ovarian cells.
- Intercellular communication within the ovarian microenvironment was amplified post-treatment.
Conclusions:
- UCMSC therapy effectively improves aged ovarian structure and function.
- The therapy modulates the ovarian microenvironment, impacting cellular senescence, DNA repair, and proliferation.
- Ubiquitin B (UBB) inhibition presents a potential therapeutic strategy for ovarian aging.