Single nuclei and spatial profiling of sacrococcygeal teratomas reveals cellular composition and X inactivation heterogeneity

Ernesto J Rojas; Krinio Giannikou; Benjamin J Huang; Soo-Jin Cho; Marco A Cordero; Deion Pena; Lan Vu; Aditya Bagrodia; S Christopher Derderian; Tippi C MacKenzie; Diana J Laird

doi:10.1038/s41698-025-01262-4

Single nuclei and spatial profiling of sacrococcygeal teratomas reveals cellular composition and X inactivation heterogeneity

NPJ Precis Oncol. 2026 Jan 21;10(1):87. doi: 10.1038/s41698-025-01262-4.

Authors

Ernesto J Rojas^{1

2

3

4

5}, Krinio Giannikou⁶, Benjamin J Huang^{4

7}, Soo-Jin Cho⁸, Marco A Cordero^{3

5

9}, Deion Pena^{10

11}, Lan Vu^{3

9}, Aditya Bagrodia⁶, S Christopher Derderian^{10

11}, Tippi C MacKenzie^{12

13

14}, Diana J Laird^{15

16

17

18}

Affiliations

¹ Department of Obstetrics, Gynecology and Reproductive Science, University of California, San Francisco, San Francisco, CA, 94143, USA.
² Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA, 94143, USA.
³ UCSF Center for Maternal-Fetal Precision Medicine, San Francisco, CA, 94143, USA.
⁴ Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, 94143, USA.
⁵ Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, 94143, USA.
⁶ Department of Urology, Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA.
⁷ Department of Pediatrics, University of California, San Francisco, San Francisco, CA, 94143, USA.
⁸ Department of Pathology, University of California, San Francisco, San Francisco, CA, 94143, USA.
⁹ Department of Surgery, University of California, San Francisco, San Francisco, CA, 94143, USA.
¹⁰ Division of Pediatric Surgery, Department of Surgery, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
¹¹ Colorado Fetal Care Center, Children's Hospital Colorado, Aurora, CO, 80045, USA.
¹² UCSF Center for Maternal-Fetal Precision Medicine, San Francisco, CA, 94143, USA. tippi.mackenzie@ucsf.edu.
¹³ Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, 94143, USA. tippi.mackenzie@ucsf.edu.
¹⁴ Department of Surgery, University of California, San Francisco, San Francisco, CA, 94143, USA. tippi.mackenzie@ucsf.edu.
¹⁵ Department of Obstetrics, Gynecology and Reproductive Science, University of California, San Francisco, San Francisco, CA, 94143, USA. diana.laird@ucsf.edu.
¹⁶ Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA, 94143, USA. diana.laird@ucsf.edu.
¹⁷ Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, 94143, USA. diana.laird@ucsf.edu.
¹⁸ Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, 94143, USA. diana.laird@ucsf.edu.

Abstract

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 exhibited biallelic expression of X-linked genes, consistent with X-inactivation failure or reactivation of the once inactivated X-chromosome. These biallelic cells were enriched for developmental and neuronal programs, whereas cells with single-allelic X-chromosome preferentially expressed immune-related genes. Biallelic X-chromosome activation, which can occur only in female cells, may result in transcriptomic features that favor survival of tumor cells, contributing to the sex bias of SCTs. Our findings reveal a link between X-chromosome inactivation and SCT cell identity, suggesting that X-dosage dysregulation may influence SCT heterogeneity and immune landscape.

Abstract

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