Brain region-specific gene signatures revealed by distinct astrocyte subpopulations unveil links to glioma and neurodegenerative diseases

Raquel Cuevas Diaz Duran, Chih Yen Wang, Hui Zheng, Benjamin Deneen, Jia Qian Wu

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Currently, there are no effective treatments for glioma or for neurodegenerative diseases because of, in part, our limited understanding of the pathophysiology and cellular heterogeneity of these diseases. Mounting evidence suggests that astrocytes play an active role in the pathogenesis of these diseases by contributing to a diverse range of pathophysiological states. In a previous study, five molecularly distinct astrocyte subpopulations from three different brain regions were identified. To further delineate the underlying diversity of these populations, we obtained mouse brain region-specific gene signatures for both protein-coding and long non-coding RNA and found that these astrocyte subpopulations are endowed with unique molecular signatures across diverse brain regions. Additional gene set and single-sample enrichment analyses revealed that gene signatures of different subpopulations are differentially correlated with glioma tumors that harbor distinct genomic alterations. To the best of our knowledge, this is the first study that links transcriptional profiles of astrocyte subpopulations with glioma genomic mutations. Furthermore, our results demonstrated that subpopulations of astrocytes in select brain regions are associated with specific neurodegenerative diseases. Overall, the present study provides a new perspective for understanding the pathophysiology of glioma and neurodegenerative diseases and highlights the potential contributions of diverse astrocyte populations to normal, malignant, and degenerative brain functions.

Original languageEnglish
Article numbere0288-18.2019
JournaleNeuro
Volume6
Issue number2
DOIs
Publication statusPublished - 2019 Mar 1

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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