Astrocyte and Microglial Transcriptional Programs in the Atypical Teratoid/Rhabdoid Tumor Microenvironment
- 1Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306, USA
- 2Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA
- 3Institute for Pediatric Rare Diseases, Florida State University, Tallahassee, FL 32306, USA
Abstract
Background/Objectives: The original GSE283839 study characterized malignant-cell heterogeneity in atypical teratoid/rhabdoid tumor (ATRT). Building on this resource, we investigated the less-characterized glial microenvironment, focusing on astrocyte and microglial transcriptional programs and expression-supported candidate interactions with tumor cells. Methods: We reanalyzed single-nucleus RNA-sequencing data from 12 ATRT tumors using published annotations, program scoring, paired astrocyte–tumor comparisons, and conservative annotation sensitivities. CellChat analyses used 10,000 permutations and within-model Benjamini–Hochberg (BH) correction. An independent cohort comprised eight specimens from four patients. Results: The discovery dataset included 47 annotated astrocytes and 288 annotated microglia. Astrocytes expressed SLC1A2, SLC1A3, and GLUL, with higher glutamate/glutamine-module scores than matched tumor cells in two of three evaluable tumors. This difference persisted in the single tumor evaluable under conservative annotation. Microglia exhibited overlapping inflammatory, immunoregulatory, phagocytic/lipid-processing, and antigen-presentation programs. Across 12 tumors, microglial CD74 expression correlated with the antigen-presentation module score. Candidate interactions included astrocyte-to-tumor NCAM1–FGFR1 and PTN–PTPRZ1 and microglia-to-tumor SPP1-related pairs. Tumor-to-microglia APP–CD74 passed within-model BH correction in 7/10 eligible discovery tumors. External analyses supported tumor-to-myeloid APP–CD74 in at least one myeloid population in each of five evaluable specimens from four patients. Conclusions: This exploratory study highlights astrocyte metabolic expression programs and immune-related microglial programs in ATRT, prioritizing APP–CD74 and additional expression-supported glia–tumor interaction candidates for future spatial and functional investigation.
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BibTeX
@article{xue2026astrocyte,
title = {{Astrocyte and Microglial Transcriptional Programs in the Atypical Teratoid/Rhabdoid Tumor Microenvironment}},
author = {Yu Xue and Uvindu Thilanka and Drishty Badhon Sarker and Md Al Azad and Qing-Xiang Amy Sang},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18213455},
url = {https://www.mdpi.com/2072-6694/18/21/3455},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Astrocyte and Microglial Transcriptional Programs in the Atypical Teratoid/Rhabdoid Tumor Microenvironment
AU - Yu Xue
AU - Uvindu Thilanka
AU - Drishty Badhon Sarker
AU - Md Al Azad
AU - Qing-Xiang Amy Sang
PY - 2026
DA - 2026/10/26
JO - Cancers
DO - 10.3390/cancers18213455
UR - https://www.mdpi.com/2072-6694/18/21/3455
AB - Background/Objectives: The original GSE283839 study characterized malignant-cell heterogeneity in atypical teratoid/rhabdoid tumor (ATRT). Building on this resource, we investigated the less-characterized glial microenvironment, focusing on astrocyte and microglial transcriptional programs and expression-supported candidate interactions with tumor cells. Methods: We reanalyzed single-nucleus RNA-sequencing data from 12 ATRT tumors using published annotations, program scoring, paired astrocyte–tumor comparisons, and conservative annotation sensitivities. CellChat analyses used 10,000 permutations and within-model Benjamini–Hochberg (BH) correction. An independent cohort comprised eight specimens from four patients. Results: The discovery dataset included 47 annotated astrocytes and 288 annotated microglia. Astrocytes expressed SLC1A2, SLC1A3, and GLUL, with higher glutamate/glutamine-module scores than matched tumor cells in two of three evaluable tumors. This difference persisted in the single tumor evaluable under conservative annotation. Microglia exhibited overlapping inflammatory, immunoregulatory, phagocytic/lipid-processing, and antigen-presentation programs. Across 12 tumors, microglial CD74 expression correlated with the antigen-presentation module score. Candidate interactions included astrocyte-to-tumor NCAM1–FGFR1 and PTN–PTPRZ1 and microglia-to-tumor SPP1-related pairs. Tumor-to-microglia APP–CD74 passed within-model BH correction in 7/10 eligible discovery tumors. External analyses supported tumor-to-myeloid APP–CD74 in at least one myeloid population in each of five evaluable specimens from four patients. Conclusions: This exploratory study highlights astrocyte metabolic expression programs and immune-related microglial programs in ATRT, prioritizing APP–CD74 and additional expression-supported glia–tumor interaction candidates for future spatial and functional investigation.
SN - 2072-6694
ER -