Journal Article

Identification of diverse astrocyte populations and their malignant analogs

Noebels, Jeffrey L, Carlson, Jeffrey, Yu, Kwanha, Hatcher, Asante, Creighton, Chad J, John Lin, Chia-Ching, Lee, Hyun Kyoung, Weston, Matthew C, Mohila, Carrie A, Zhang, Yiqun, Arenkiel, Benjamin R, Patel, Akash J, Huang, Teng-Wei, Deneen, Benjamin, Zhu, Wenyi, Chen, Fengju, Ahmed, Nabil

2017

Overview

The nature of astrocyte diversity in the adult brain has remained poorly defined. The authors identify five astrocyte subpopulations in the brain that exhibit extensive molecular and functional diversity. They uncover correlative populations in malignant glioma, providing insight into how diverse astrocyte populations contribute to synaptogenesis, tumor pathophysiology and neurological disease. Astrocytes are the most abundant cell type in the brain, where they perform a wide array of functions, yet the nature of their cellular heterogeneity and how it oversees these diverse roles remains shrouded in mystery. Using an intersectional fluorescence-activated cell sorting–based strategy, we identified five distinct astrocyte subpopulations present across three brain regions that show extensive molecular diversity. Application of this molecular insight toward function revealed that these populations differentially support synaptogenesis between neurons. We identified correlative populations in mouse and human glioma and found that the emergence of specific subpopulations during tumor progression corresponded with the onset of seizures and tumor invasion. In sum, we have identified subpopulations of astrocytes in the adult brain and their correlates in glioma that are endowed with diverse cellular, molecular and functional properties. These populations selectively contribute to synaptogenesis and tumor pathophysiology, providing a blueprint for understanding diverse astrocyte contributions to neurological disease.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 42/109 / 45 / 45/91 / 631/378/2596/1308 / 631/67/1922 / 64 / 64/60 / Aldehyde Dehydrogenase - metabolism / Animal Genetics and Genomics / Animals / Artificial chromosomes / Astrocytes / Astrocytes - metabolism / Astrocytes - physiology / Behavioral Sciences / Biological Techniques / Biomedicine / Brain / Brain - metabolism / Care and treatment / Coculture Techniques / Development and progression / Female / Flow Cytometry / Glioma - metabolism / Glioma - physiopathology / Gliomas / Humans / Male / Medical schools / Medicine / Mice / Mice, Transgenic / Morphology / Neurobiology / Neurons - physiology / Neurophysiology / Neurosciences / Oxidoreductases Acting on CH-NH Group Donors / Pathophysiology / Physiological aspects / Seizures - physiopathology / Synapses - physiology / Transcriptome