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Cell Rep. 2019 Feb 26;26(9):2477-2493.e9. doi: 10.1016/j.celrep.2019.02.003.

Cell-Type-Specific Gene Expression Profiling in Adult Mouse Brain Reveals Normal and Disease-State Signatures.

Author information

1
Department of Clinical Neurosciences, Laboratory of Neurotherapies and Neuromodulation (LNTM), Lausanne University Hospital, 1011 Lausanne, Switzerland; Neuroscience Research Center, LNTM, Lausanne University Hospital, 1011 Lausanne, Switzerland.
2
Department of Physiology, Laboratory of Neuroenergetics, University of Lausanne, 1005 Lausanne, Switzerland.
3
University of Strasbourg, CNRS, UMR 7364, Laboratory of Cognitive and Adaptive Neuroscience, 67000 Strasbourg, France.
4
Sorbonnes Université, Centre National de la Recherche Scientifique, Research Unit Biology of Adaptation and Aging, Team Compensation in Neurodegenerative Diseases and Aging, 75252 Paris, France.
5
Department of Fundamental Neurosciences, University of Lausanne, 1005 Lausanne, Switzerland.
6
University of Strasbourg, CNRS, INSERM, UMR 7104, Microarray and Sequencing Platform, Institute of Genetic and Molecular and Cellular Biology, 67404 Illkirch, France.
7
Centre for Brain Research, Faculty of Medical and Health Science, The University of Auckland, Auckland 1023, New Zealand.
8
Department of Physiology, Laboratory of Neuroenergetics, University of Lausanne, 1005 Lausanne, Switzerland; Centre de Résonance Magnétique des Systèmes Biologiques UMR 5536, CNRS-Université de Bordeaux, 146 rue Léo Saignat, Bordeaux, France.
9
Department of Fundamental Neurosciences, University of Lausanne, 1005 Lausanne, Switzerland; Cellular Imaging Facility, University of Lausanne, 1005 Lausanne, Switzerland.
10
Department of Clinical Neurosciences, Laboratory of Neurotherapies and Neuromodulation (LNTM), Lausanne University Hospital, 1011 Lausanne, Switzerland; Neuroscience Research Center, LNTM, Lausanne University Hospital, 1011 Lausanne, Switzerland. Electronic address: nicole.deglon@chuv.ch.

Abstract

The role of brain cell-type-specific functions and profiles in pathological and non-pathological contexts is still poorly defined. Such cell-type-specific gene expression profiles in solid, adult tissues would benefit from approaches that avoid cellular stress during isolation. Here, we developed such an approach and identified highly selective transcriptomic signatures in adult mouse striatal direct and indirect spiny projection neurons, astrocytes, and microglia. Integrating transcriptomic and epigenetic data, we obtained a comprehensive model for cell-type-specific regulation of gene expression in the mouse striatum. A cross-analysis with transcriptomic and epigenomic data generated from mouse and human Huntington's disease (HD) brains shows that opposite epigenetic mechanisms govern the transcriptional regulation of striatal neurons and glial cells and may contribute to pathogenic and compensatory mechanisms. Overall, these data validate this less stressful method for the investigation of cellular specificity in the adult mouse brain and demonstrate the potential of integrative studies using multiple databases.

KEYWORDS:

HD patients; HD transgenic mice; Huntington’s disease; cell-type-specific profiling; epigenetics; striatum; transcriptomics

PMID:
30811995
DOI:
10.1016/j.celrep.2019.02.003
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