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The temporal architecture of the seminiferous epithelial cycle revealed by spatial transcriptomics - PubMed

2 days ago
  • #Sertoli cells
  • #seminiferous epithelial cycle
  • #spatial transcriptomics
  • Spatial transcriptomics (seqFISH+) analyzed 867,062 mouse testis cells across 2,653 genes to reveal transcriptional patterns in seminiferous tubules, enabling high-resolution temporal mapping of the epithelial cycle.
  • Sertoli cells exhibit a cyclic transcriptional profile synchronized with spermatogenesis, which persists in germ-cell-depleted testes (busulfan and W/Wv), indicating an intrinsic cyclic program, though with reduced amplitude and gene-specific dephasing.
  • Retinoic acid (RA) acts as a permissive signal; germ-cell-depleted Sertoli cells cycle RA enzymes, and inhibition of RA synthesis via WIN 18,446 arrests the cycle mid-phase, highlighting RA's role in regulating the cycle.
  • Bidirectional signaling between germ cells and Sertoli cells was identified through ligand-receptor analysis, and Wnt inhibition with LGK974 partially mimics dephasing and amplitude changes seen in germ-cell depletion.
  • An integrative model is proposed where an intrinsic Sertoli program maintains baseline periodicity, while signals from germ cells refine and coordinate the spermatogenic cycle.