ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
X-Linked Gene Dosage and SOX2 Act as Key Roadblocks for Human Germ Cell Specification in Klinefelter Syndrome.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
4 citing papers in PubMed.
- Decomposing population differences in type 2 diabetes through a high-resolution GWAS of ~600,000 individuals with East Asian ancestry.Communications biology · 2026Article
- The road to restore male fertility using in vitro-derived germ cells.Human reproduction update · 2026Review
- Conference report: current advances in embryo model research at the International Dutch Embryo Model Meeting 2025.Biology open · 2026Article
- X-Linked Gene Dosage and SOX2 Act as Key Roadblocks for Human Germ Cell Specification in Klinefelter Syndrome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
Klinefelter syndrome (KS), characterized by the presence of at least one extra X-chromosome, is a common cause of male infertility. However, the mechanism underlying the failure of germline specification is not well studied. Intriguingly, the differentiation efficiency of female human pluripotent stem cells (hPSCs) is often lower than that of male. This study investigates how X-linked gene dosage affects human primordial germ cell-like cells (hPGCLCs) specification in both healthy and diseased conditions. This work reveals that X-linked genes play a multifaceted role against the fate competency to hPGCLCs, with escape genes IGSF1 and CHRDL1 inhibiting the TGF-beta/Activin A and BMP pathways, respectively. Notably, this work identifies a previously unrecognized role of SOX2, upregulated by the escape gene USP9X, elucidating a species-specific function in the mammalian germline. The USP9X-SOX2 regulatory axis profoundly influenced cellular metabolism, mitochondrial morphology, and progenitor competence in hPGCLCs specification. Furthermore, the inability to downregulate SOX2 and upregulate SOX17 in response to BMP signaling impedes downstream gene activation due to motif binding competition. These findings shed novel insights into the human germline specification by elucidating the divergent roles of SOX2 versus SOX17 in mammals, influenced by X-linked gene dosage effects. These results offer potential applications for improving the induction efficiency of hPGCLCs, facilitating disease mechanistic studies.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.