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A tumor-associated photoreceptor signature unifies distinct central nervous system malignancies [Methylation array]

ABSTRACT: Mouse tumor methylation profiling by MouseMethylation Beadchips (MM285) platform

ORGANISM(S): Mus musculus

PROVIDER: GSE312950 | GEO | 2026/02/07

REPOSITORIES: GEO

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A tumor-associated photoreceptor signature unifies distinct central nervous system malignancies

Project description:This SuperSeries is composed of the SubSeries listed below.

2026-02-07 | GSE275307 | GEO

A tumor-associated photoreceptor signature unifies distinct central nervous system malignancies [bulkRNA-seq]

Project description:Pineoblastoma is a clinically aggressive childhood brain tumor that segregates into molecularly distinct subgroups. Mechanisms governing pineoblastoma pathogenesis, including developmental origins, remain poorly defined. Herein, we resolved the cellular composition of pineoblastoma and other pineal parenchymal tumors at single-cell resolution, aligning malignant cells with pineal gland development to retrace cellular origins. Integrative computational analyses mapped divergent pineoblastoma subgroups to cycling progenitors of the pinealocyte lineage. Lineage-specific perturbation of suspected drivers provoked the generation of genetically accurate preclinical models representing distinct molecular subgroups, while uncovering an oncogenic photoreceptor program conserved across pineoblastoma, retinoblastoma, and Group 3 medulloblastoma. Transcriptional activity of this program was acquired from cellular origin, incriminating photoreceptor identity as a common developmental vulnerability, substantiated as a strong dependency. Illuminated through multidisciplinary analysis of an uncommon, heterogeneous pediatric brain tumor, these advances motivate future studies evaluating developmentally encoded transcriptional programs of malignancy as potential therapeutic liabilities in clinically challenging entities.

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A tumor-associated photoreceptor signature unifies distinct central nervous system malignancies [scRNA-seq]

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A tumor-associated photoreceptor signature unifies distinct central nervous system malignancies [ATAC-seq]

Project description:Pineoblastoma is a clinically aggressive childhood brain tumor composed of distinct molecular subgroups with divergent driver genes, demographics, and clinical outcomes. To identify developmental origins and mechanisms governing disease pathogenesis, we derive single-cell transcriptomes from pineal parenchymal tumors, aligning malignant cells with developmental counterparts to retrace cellular origins. Integrative computational analyses map pineoblastoma origins to transient, cycling pinealocyte progenitors during development. Lineage-specific perturbation of suspected drivers in the early pineal gland yields preclinical models representative of consensus molecular subgroups. Multi-omic characterization of patient tumors and these models uncovers a tumor-associated photoreceptor signature (TAPS) common to pineoblastoma, retinoblastoma, and Group 3 medulloblastoma. Transcriptional activity of this signature within respective cellular origins establishes a developmental basis for molecular similarities between entities. Photoreceptor signature constituents are selective dependencies across these anatomically distinct central nervous system malignancies, motivating future studies evaluating developmentally encoded programs of malignancy as potential therapeutic liabilities.

2026-02-07 | GSE318234 | GEO

A tumor-associated photoreceptor signature unifies distinct central nervous system malignancies [Methylation array]

Project description:A tumor-associated photoreceptor signature unifies distinct central nervous system malignancies [Methylation array]

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A tumor-associated photoreceptor signature unifies distinct central nervous system malignancies

Project description:A tumor-associated photoreceptor signature unifies distinct central nervous system malignancies

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A tumor-associated photoreceptor signature unifies distinct central nervous system malignancies [bulkRNA-seq]

Project description:A tumor-associated photoreceptor signature unifies distinct central nervous system malignancies [bulkRNA-seq]

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A tumor-associated photoreceptor signature unifies distinct central nervous system malignancies [scRNA-seq]

Project description:A tumor-associated photoreceptor signature unifies distinct central nervous system malignancies [scRNA-seq]

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A tumor-associated photoreceptor signature unifies distinct central nervous system malignancies [ATAC-seq]

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Heme Oxygenase-1 in Central Nervous System Malignancies.

Project description:Central nervous system tumors are the most common pediatric solid tumors and account for 20%-25% of all childhood malignancies. Several lines of evidence suggest that brain tumors show altered redox homeostasis that triggers the activation of various survival pathways, leading to disease progression and chemoresistance. Among these pathways, heme oxygenase-1 (HO-1) plays an important role. HO-1 catalyzes the enzymatic degradation of heme with the simultaneous release of carbon monoxide (CO), ferrous iron (Fe2+), and biliverdin. The biological effects of HO-1 in tumor cells have been shown to be cell-specific since, in some tumors, its upregulation promotes cell cycle arrest and cellular death, whereas, in other neoplasms, it is associated with tumor survival and progression. This review focuses on the role of HO-1 in central nervous system malignancies and the possibility of exploiting such a target to improve the outcome of well-established therapeutic regimens. Finally, several studies show that HO-1 overexpression is involved in the development and resistance of brain tumors to chemotherapy and radiotherapy, suggesting the use of HO-1 as an innovative therapeutic target to overcome drug resistance. The following keywords were used to search the literature related to this topic: nuclear factor erythroid 2 p45-related factor 2, heme oxygenase, neuroblastoma, medulloblastoma, meningioma, astrocytoma, oligodendroglioma, glioblastoma multiforme, and gliomas.

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