ArticleAmerican journal of human genetics2021
Comparative single-cell analysis of biopsies clarifies pathogenic mechanisms in Klinefelter syndrome.
Article in American journal of human genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 2 of them syntheses that pooled it.
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Who cites it
50 citing papers in PubMed, 2 syntheses or guidelines pooled it, 71 citations in OpenAlex.
- Sex chromosome aneuploidy impacts on human gene expression and regulation: a systematic review.Molecular medicine (Cambridge, Mass.) · 2025Pooled it
- Genetic and genomic insights into male reproductive tract development.Fertility and sterility · 2025Pooled it
- Epigenetic dynamics of human spermatogenesis and their dysregulation in non-obstructive azoospermia.Protein & cell · 2026Article
- Comprehensive profiling of cell-free RNA in seminal plasma reveals functional links to spermatogenic impairment.Clinical and translational medicine · 2026Article
- Single-cell analysis of fetal testis reveals dysfunction of human Leydig cells in Klinefelter syndrome.The Journal of clinical investigation · 2026Article
- Mapping whole-organism genetic comorbidities across model Species using unified ontologies.Genetics · 2026Article
- Endothelial PDGF Signaling Dysregulation Impairs Testicular Interstitial Homeostasis in Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Testis Molecular Pathways in CAIS Unveil Testosterone/Estradiol on Germ Cell Tumor Risk in Non-Obstructive Azoospermia.The Journal of clinical endocrinology and metabolism · 2026Article
- Whole genome sequencing approach for the detection of rare protein-altering variants associated with familial male infertility.The Egyptian journal of medical human genetics · 2025Article
- A comparison of spermatogenesis between flies and men-conserved processes of male gamete production.Human reproduction update · 2025Review
- POU4F2/Brn-3b is Essential for Spermatogenesis and its Disruption is Linked to Male Infertility in Mice and Humans.Research square · 2025Article
- Aging-TCA: a cross-species single-cell transcriptomic atlas for studying testicular aging.BMC genomics · 2025Article
- The human infertility single-cell testis atlas (HISTA): an interactive molecular scRNA-Seq reference of the human testis.Andrology · 2025Article
- An extra X chromosome: dissecting its role in male fetal germ cell maturation.Science China. Life sciences · 2025Article
- Anatomical considerations, testicular, and scrotal anatomy of nonobstructive azoospermia patients.Asian journal of andrology · 2025Review
- Divergent B-cell and cytotoxic TNK cell activation signatures in HLA-B27-associated ankylosing spondylitis and acute anterior uveitis.Frontiers in immunology · 2025Article
- Sertoli cells as a hub in testicular development and male reproductive.Frontiers in cell and developmental biology · 2025Review
- Single-cell sequencing in non-obstructive azoospermia: insights from primary and re-analysis studies.Frontiers in endocrinology · 2025Review
- Article
- Temporal maturation of Sertoli cells during the establishment of the cycle of the seminiferous epithelium†.Biology of reproduction · 2024Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Klinefelter syndrome (KS), also known as 47, XXY, is characterized by a distinct set of physiological abnormalities, commonly including infertility. The molecular basis for Klinefelter-related infertility is still unclear, largely because of the cellular complexity of the testis and the intricate endocrine and paracrine signaling that regulates spermatogenesis. Here, we demonstrate an analysis framework for dissecting human testis pathology that uses comparative analysis of single-cell RNA-sequencing data from the biopsies of 12 human donors. By comparing donors from a range of ages and forms of infertility, we generate gene expression signatures that characterize normal testicular function and distinguish clinically distinct forms of male infertility. Unexpectedly, we identified a subpopulation of Sertoli cells within multiple individuals with KS that lack transcription from the XIST locus, and the consequence of this is increased X-linked gene expression compared to all other KS cell populations. By systematic assessment of known cell signaling pathways, we identify 72 pathways potentially active in testis, dozens of which appear upregulated in KS. Altogether our data support a model of pathogenic changes in interstitial cells cascading from loss of X inactivation in pubertal Sertoli cells and nominate dosage-sensitive factors secreted by Sertoli cells that may contribute to the process. Our findings demonstrate the value of comparative patient analysis in mapping genetic mechanisms of disease and identify an epigenetic phenomenon in KS Sertoli cells that may prove important for understanding causes of infertility and sex chromosome evolution.
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