A longitudinal single-cell and spatial multiomic atlas of pediatric high-grade glioma.
| العنوان: | A longitudinal single-cell and spatial multiomic atlas of pediatric high-grade glioma. |
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| المؤلفون: | Sussman JH; Medical Scientist Training Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.; Graduate Group in Genomics and Computational Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Oldridge DA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA., Yu W; Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA., Chen CH; Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA., Zellmer AM; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA., Rong J; Graduate Group in Genomics and Computational Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.; Department of Statistics and Data Science, University of Pennsylvania, Philadelphia, PA., Parvaresh-Rizi A; Department of Biomedical Engineering, University of Rhode Island, Kingston, RI., Thadi A; Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA., Xu J; Medical Scientist Training Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.; Graduate Group in Genomics and Computational Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Bandyopadhyay S; Medical Scientist Training Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.; Cellular and Molecular Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, PA., Sun Y; Medical Scientist Training Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.; Neuroscience Graduate Group, Perelman School of Medicine, University of Pennsylvania, PA., Wu D; Medical Scientist Training Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.; Graduate Group in Genomics and Computational Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Emerson Hunter C; Medical Scientist Training Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.; Graduate Group in Genomics and Computational Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Brosius S; Graduate Group in Genomics and Computational Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Ahn KJ; Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA., Baxter AE; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA., Koptyra MP; Department of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA., Vanguri RS; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA., McGrory S; Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA., Resnick AC; Department of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA., Storm PB; Department of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA., Amankulor NM; Department of Neurosurgery, Perelman School of Medicine, Philadelphia, PA., Santi M; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA., Viaene AN; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA., Zhang N; Department of Statistics and Data Science, University of Pennsylvania, Philadelphia, PA., Raedt T; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.; Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA., Cole K; Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA., Tan K; Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA.; Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.; Center for Single Cell Biology, Children's Hospital of Philadelphia, Philadelphia, PA. |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2024 Mar 08. Date of Electronic Publication: 2024 Mar 08. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | Pediatric high-grade glioma (pHGG) is an incurable central nervous system malignancy that is a leading cause of pediatric cancer death. While pHGG shares many similarities to adult glioma, it is increasingly recognized as a molecularly distinct, yet highly heterogeneous disease. In this study, we longitudinally profiled a molecularly diverse cohort of 16 pHGG patients before and after standard therapy through single-nucleus RNA and ATAC sequencing, whole-genome sequencing, and CODEX spatial proteomics to capture the evolution of the tumor microenvironment during progression following treatment. We found that the canonical neoplastic cell phenotypes of adult glioblastoma are insufficient to capture the range of tumor cell states in a pediatric cohort and observed differential tumor-myeloid interactions between malignant cell states. We identified key transcriptional regulators of pHGG cell states and did not observe the marked proneural to mesenchymal shift characteristic of adult glioblastoma. We showed that essential neuromodulators and the interferon response are upregulated post-therapy along with an increase in non-neoplastic oligodendrocytes. Through in vitro pharmacological perturbation, we demonstrated novel malignant cell-intrinsic targets. This multiomic atlas of longitudinal pHGG captures the key features of therapy response that support distinction from its adult counterpart and suggests therapeutic strategies which are targeted to pediatric gliomas. Competing Interests: Competing interests The authors declare no competing interests. |
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| معلومات مُعتمدة: | F30 CA268782 United States CA NCI NIH HHS; T32 CA009140 United States CA NCI NIH HHS; T32 GM007170 United States GM NIGMS NIH HHS; F30 CA277965 United States CA NCI NIH HHS; R38 HL143613 United States HL NHLBI NIH HHS; U2C CA233285 United States CA NCI NIH HHS; U54 HL165442 United States HL NHLBI NIH HHS |
| تواريخ الأحداث: | Date Created: 20240318 Latest Revision: 20240425 |
| رمز التحديث: | 20240425 |
| مُعرف محوري في PubMed: | PMC10942465 |
| DOI: | 10.1101/2024.03.06.583588 |
| PMID: | 38496580 |
| قاعدة البيانات: | MEDLINE |
| DOI: | 10.1101/2024.03.06.583588 |
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