ArticleCell & bioscience2025
Single-cell transcriptomics of organoids reveals transcriptional control of germline stem cell fate by an E2F1-TFAP2C-SOX17 positive-feedback loop in Turner syndrome.
Article in Cell & bioscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundTurner syndrome is the most common sex chromosome abnormality in females and affects approximately 1-2 in 2500 girls and women. To date, no cure is available for the treatment of infertility in Turner syndrome patients with 45,XO.
resultsHere, we report an organoid approach for generating human germline stem cells and their somatic niche cells in the Turner syndrome. The niche provides an appropriate microenvironment for germline fate in the organoids. Single-cell transcriptomics reveals the dynamics of germline development from iPSCs to germline stem cells, together with their somatic niche. The germline stem cells follow a successive trajectory of four developmental states with featured molecular events, which determine the developmental fate of the germline stem cells. Notably, we have identified the key factor E2F1 from the germline trajectory to regulate the germline stemness fate. E2F1 knockout impairs the specification of the germline stem cells in 45,XO organoids. Remarkably, E2F1 acts as a key fate regulator by activating the transcription of germline factor TFAP2C through binding to and activating its promoter. Importantly, transcriptional regulation of E2F1 creates a positive-feedback loop of E2F1-TFAP2C-SOX17, which contributes to the fate of the germline stem cells, hPGCLCs.
conclusionThis study revealed a successive development trajectory of germline stem cells and identified E2F1 and related positive-feedback loop of E2F1-TFAP2C-SOX17 to control the fate of germline stem cells, hPGCLCs, offering a foundation for understanding and reconstituting germline fate in vitro in Turner syndrome patients with 45,XO.
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