biostudies-literatureRojas EJNational Center for Advancing Translational SciencesNCATS NIH HHSChan Zuckerberg BiohubUCSF Center for Maternal Fetal MedicineNIH NCI87https://www.ebi.ac.uk/biostudies/studies/S-EPMC12949016biostudies-literatureUnknown10(1)Sacrococcygeal teratomas (SCTs) are the most common neonatal tumors, yet their cellular origins, clinical stratification, and sex bias-occurring three times more in XX than XY individuals-remain poorly understood. To address these gaps, we examined six postnatal (one male and five female) and two prenatal (both female) SCTs by single nuclei RNA-seq and spatial transcriptomics. We identified five broad cellular lineages in SCTs: stroma, epithelia, endothelia, neuroectoderm, and immune. The transcriptomes and lineage compositions showed significant heterogeneity, which offer a framework for future molecular stratification. SCTs are thought to originate from and be propagated by pluripotent cells, notably however, we did not detect these populations. Among female tumors, a subset of cells exhNPJ precision oncologySingle nuclei and spatial profiling of sacrococcygeal teratomas reveals cellular composition and X inactivation heterogeneity.PMC12949016F31-CA284719UL1 TR001872Bagrodia AVu LRojas EJDerderian SCLaird DJHuang BJPena DGiannikou KCho SJCordero MAMacKenzie TCfalseSingle nuclei and spatial profiling of sacrococcygeal teratomas reveals cellular composition and X inactivation heterogeneity.Sacrococcygeal teratomas (SCTs) are the most common neonatal tumors, yet their cellular origins, clinical stratification, and sex bias-occurring three times more in XX than XY individuals-remain poorly understood. To address these gaps, we examined six postnatal (one male and five female) and two prenatal (both female) SCTs by single nuclei RNA-seq and spatial transcriptomics. We identified five broad cellular lineages in SCTs: stroma, epithelia, endothelia, neuroectoderm, and immune. The transcriptomes and lineage compositions showed significant heterogeneity, which offer a framework for future molecular stratification. SCTs are thought to originate from and be propagated by pluripotent cells, notably however, we did not detect these populations. Among female tumors, a subset of cells exh2026-01-01T00:00:00Z2026 Jan2026-07-16T23:33:24.744Z2026-07-12T03:11:24.746ZS-EPMC129490164156573910.1038/s41698-025-01262-4