ArticleNature communications2025
NR2F2 regulation of interstitial cell fate in the embryonic mouse testis and its impact on differences of sex development.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Advances in the Molecular Regulatory Mechanisms of Testicular Development and Spermatogenesis in Yaks.Animals : an open access journal from MDPI · 2026Review
- Post-translational modification of proteins in the human testis development pathway.Human reproduction update · 2026Review
- Specification of the interstitial cell lineage in the fetal mouse ovary requires balanced Notch signaling.bioRxiv : the preprint server for biology · 2026Article
- NR2F2/AGAP2 axis: regulating lipid synthesis to drive AML progression via AMPKα/ACC pathway.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Targeting CDH13 as a therapeutic strategy to mitigate pathological ocular angiogenesis.Journal of translational medicine · 2026Article
- Generation of functionally competent testicular somatic cells from pluripotent stem cells.Science advances · 2026Article
- The role of NR2F2 in cancer (Review).Oncology letters · 2025Review
- Identification of Key Differentially Expressed Genes During Early Sex Determination in Chicken Embryos.International journal of molecular sciences · 2025Article
- Ovarian development is driven by early spatiotemporal priming of the coelomic epithelium.bioRxiv : the preprint server for biology · 2025Article
- Generation of a Nr2f2-driven inducible Cre mouse to target interstitial cells in the reproductive system†.Biology of reproduction · 2025Article
- Article
- NEDD4 Promotes Sertoli Cell Proliferation and Adult Leydig Cell Differentiation in the Murine Testis.Endocrinology · 2025Article
- Single-cell atlas of human skin implicates APOE pro-inflammatory signaling in diabetic foot ulcers.Frontiers in immunology · 2025Article
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8 authors.
Funding
Abstract
Testicular fetal Leydig cells produce androgens essential for male reproductive development. Impaired fetal Leydig cell differentiation leads to differences of sex development including hypospadias, cryptorchidism, and infertility. Despite fetal Leydig cells are thought to originate from proliferating progenitor cells in the testis interstitium, the precise mechanisms governing the interstitial cells to fetal Leydig cell transition remain elusive. Using mouse models and single-nucleus multiomics, we find that fetal Leydig cells arise from a Nr2f2-positive interstitial population. Embryonic deletion of Nr2f2 in mouse testes results in differences of sex development, including dysgenic testes, Leydig cell hypoplasia, cryptorchidism, and hypospadias. By combining single-nucleus multiomics and NR2F2 ChIP-seq we find that NR2F2 promotes the progenitor fate while suppresses Leydig cell differentiation by modulating key transcription factors and downstream genes. Our findings establish Nr2f2 as a crucial regulator of fetal Leydig cell differentiation and provide molecular insights into differences of sex development linked to Nr2f2 mutations.
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