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Heng, D.* ; Jin, K.* ; Yin, G.* ; Tian, C. ; Sheng, X.* ; Lu, J.* ; Wu, Y.* ; Ye, X.* ; Shi, P.* ; Li, H.* ; Liu, C.* ; Liu, L.* ; Zhu, Z.*

Reprogramming senescent granulosa cells for germ-cell generation.

Sci. China Life Sci., 14 (2026)
DOI PMC
Oocyte number and quality decline greatly with age. Previously, we demonstrated that granulosa cells (GCs) from young mice could be effectively reprogrammed into chemically induced pluripotent stem cells (GC-CiPSCs), which can generate functional oocytes. Here, we investigated whether GCs isolated from reproductively-aged mice could similarly generate germ cells. Old GC-CiPSCs reprogrammed from GCs isolated from reproductively-aged mice exhibited pluripotent gene expression profiles comparable to those of embryonic stem cells and young GC-CiPSCs. However, old GC-CiPSCs displayed compromised mitochondrial function and a reduced capacity to differentiate into primordial germ cell-like cells (PGCLCs). Mitochondrial enhancement did not improve PGCLC induction efficiency in old GC-CiPSCs. However, inhibiting the ERK/MAPK signaling pathway improved the induction efficiency of PGCLCs from old GC-CiPSCs. These findings demonstrate functional deficits in generating PGCLCs from aged mouse GC-derived iPSCs and identify a strategy to improve PGCLC induction efficiency from senescent GCs.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Erk ; Chemical Reprogramming ; Granulosa Cells ; Mitochondria ; Primordial Germ Cell ; Senescence; Somatic-cells; Stem-cells; Mitochondrial Fission; Pluripotency; Fertility; Specification; Induction; Dynamics; Promotes; Pathway
ISSN (print) / ISBN 1006-9305
e-ISSN 1862-2798
Journal Science China - Life Sciences
Quellenangaben Volume: , Issue: , Pages: 14 Article Number: , Supplement: ,
Publisher Springer
Publishing Place 16 Donghuangchenggen North St, Beijing 100717, Peoples R China
Reviewing status Peer reviewed
Institute(s) Institute of Transl. Stem Cell Research (ITS)
Grants National Key Research and Development Program of China
National Natural Science Foundation of China