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Pluripotency factor Tex10 finetunes Wnt signaling for spermatogenesis and primordial germ cell development

Author

Listed:
  • Feifei Yuan

    (Columbia University Irving Medical Center)

  • Jihong Yang

    (Columbia University Irving Medical Center
    BoYu Intelligent Health Innovation Laboratory)

  • Fanglin Ma

    (Icahn School of Medicine at Mount Sinai)

  • Zhe Hu

    (Columbia University Irving Medical Center)

  • Vikas Malik

    (Columbia University Irving Medical Center)

  • Ruge Zang

    (Columbia University Irving Medical Center)

  • Dan Li

    (Columbia University Irving Medical Center)

  • Xianle Shi

    (Columbia University Irving Medical Center)

  • Xin Huang

    (Columbia University Irving Medical Center)

  • Hongwei Zhou

    (Columbia University Irving Medical Center)

  • Jianlong Wang

    (Columbia University Irving Medical Center)

Abstract

Testis-specific transcript 10 (Tex10) is highly expressed in the testis, embryonic stem cells (ESCs), and primordial germ cells (PGCs). We previously generated a Tex10 knockout mouse model demonstrating its critical roles in ESC pluripotency and preimplantation development. Here, using conditional knockout mice and dTAG-degron ESCs, we show Tex10 is required for spermatogenesis and ESC-to-PGCLC differentiation. Specifically, Tex10-null spermatocytes arrest at metaphase I, compromising round spermatid formation. Tex10 depletion and overexpression compromise and enhance ESC-to-PGCLC differentiation, respectively. Mechanistically, bulk and single-cell RNA sequencing reveals that Tex10 depletion downregulates genes involved in pluripotency, PGC development, and spermatogenesis while upregulating genes promoting somatic programs. Chromatin occupancy study reveals that Tex10 binds to H3K4me3-marked promoters of Psmd3 and Psmd7, negative regulators of Wnt signaling, and activates their expression, thereby restraining Wnt signaling. Our study identifies Tex10 as a previously unappreciated factor in spermatogenesis and PGC development, offering potential therapeutic insights for treating male infertility.

Suggested Citation

  • Feifei Yuan & Jihong Yang & Fanglin Ma & Zhe Hu & Vikas Malik & Ruge Zang & Dan Li & Xianle Shi & Xin Huang & Hongwei Zhou & Jianlong Wang, 2025. "Pluripotency factor Tex10 finetunes Wnt signaling for spermatogenesis and primordial germ cell development," Nature Communications, Nature, vol. 16(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57165-2
    DOI: 10.1038/s41467-025-57165-2
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