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  3. Spatiotemporal transcriptomic changes of human ovarian aging and the regulatory role of FOXP1

Spatiotemporal transcriptomic changes of human ovarian aging and the regulatory role of FOXP1

  • Nat Aging. 2024 Apr;4(4):527-545. doi: 10.1038/s43587-024-00607-1.
Meng Wu # 1 2 3,  Weicheng Tang # 1 2 3,  Ying Chen 1 2 3,  Liru Xue 1 2 3,  Jun Dai 4 5 6,  Yan Li 7 8 9,  Xiaoran Zhu 1 2 3,  Chuqing Wu 1 2 3,  Jiaqiang Xiong 10,  Jinjin Zhang 1 2 3,  Tong Wu 1 2 3,  Su Zhou 1 2 3,  Dan Chen 1 2 3,  Chaoyang Sun 1 2 3,  Jing Yu 11,  Hongyi Li 12,  Yican Guo 1 2 3,  Yibao Huang 1 2 3,  Qingqing Zhu 1 2 3,  Simin Wei 1 2 3,  Ziliang Zhou 13,  Mingfu Wu 1 2 3,  Ya Li 1 2 3,  Tao Xiang 1 2 3,  Huiying Qiao 14,  Shixuan Wang 15 16 17
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, China.
  • 3 Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, China.
  • 4 Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. jundai@tjh.tjmu.edu.cn.
  • 5 National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, China. jundai@tjh.tjmu.edu.cn.
  • 6 Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, China. jundai@tjh.tjmu.edu.cn.
  • 7 Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. liyan@tjh.tjmu.edu.cn.
  • 8 National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, China. liyan@tjh.tjmu.edu.cn.
  • 9 Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, China. liyan@tjh.tjmu.edu.cn.
  • 10 Department of Obstetrics and Gynecology, Zhongnan Hospital, Wuhan University, Wuhan, China.
  • 11 Shanghai Health Commission Key Lab of Artificial Intelligence (AI)-Based Management of Inflammation and Chronic Diseases, Sino-French Cooperative Central Lab, Shanghai Pudong Gongli Hospital, Secondary Military Medical University, Shanghai, China.
  • 12 College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, China.
  • 13 College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, China.
  • 14 Shanghai Ocean University, Shanghai, China.
  • 15 Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. shixuanwang@tjh.tjmu.edu.cn.
  • 16 National Clinical Research Center for Obstetrical and Gynecological Diseases, Wuhan, China. shixuanwang@tjh.tjmu.edu.cn.
  • 17 Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan, China. shixuanwang@tjh.tjmu.edu.cn.
  • # Contributed equally.
PMID: 38594460 DOI: 10.1038/s43587-024-00607-1
Abstract

Limited understanding exists regarding how aging impacts the cellular and molecular aspects of the human ovary. This study combines single-cell RNA Sequencing and spatial transcriptomics to systematically characterize human ovarian aging. Spatiotemporal molecular signatures of the eight types of ovarian cells during aging are observed. An analysis of age-associated changes in gene expression reveals that DNA damage response may be a key biological pathway in oocyte aging. Three granulosa cells subtypes and five theca and stromal cells subtypes, as well as their spatiotemporal transcriptomics changes during aging, are identified. FOXP1 emerges as a regulator of ovarian aging, declining with age and inhibiting CDKN1A transcription. Silencing FOXP1 results in premature ovarian insufficiency in mice. These findings offer a comprehensive understanding of spatiotemporal variability in human ovarian aging, aiding the prioritization of potential diagnostic biomarkers and therapeutic strategies.

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