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Nat Neurosci. 2019 Oct;22(10):1696-1708. doi: 10.1038/s41593-019-0491-3. Epub 2019 Sep 24.

Single-cell transcriptomic profiling of the aging mouse brain.

Author information

1
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA. methodios_ximerakis@harvard.edu.
2
Harvard Stem Cell Institute, Cambridge, MA, USA. methodios_ximerakis@harvard.edu.
3
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA. methodios_ximerakis@harvard.edu.
4
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
5
Harvard Stem Cell Institute, Cambridge, MA, USA.
6
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.
7
Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
8
The Donnelly Centre, University of Toronto, Toronto, ON, Canada.
9
Bauer Core, Faculty of Arts and Sciences Division of Science, Harvard University, Cambridge, MA, USA.
10
BioMicro Center, Massachusetts Institute of Technology, Cambridge, MA, USA.
11
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA. lee_rubin@harvard.edu.
12
Harvard Stem Cell Institute, Cambridge, MA, USA. lee_rubin@harvard.edu.
13
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA. lee_rubin@harvard.edu.

Abstract

The mammalian brain is complex, with multiple cell types performing a variety of diverse functions, but exactly how each cell type is affected in aging remains largely unknown. Here we performed a single-cell transcriptomic analysis of young and old mouse brains. We provide comprehensive datasets of aging-related genes, pathways and ligand-receptor interactions in nearly all brain cell types. Our analysis identified gene signatures that vary in a coordinated manner across cell types and gene sets that are regulated in a cell-type specific manner, even at times in opposite directions. These data reveal that aging, rather than inducing a universal program, drives a distinct transcriptional course in each cell population, and they highlight key molecular processes, including ribosome biogenesis, underlying brain aging. Overall, these large-scale datasets (accessible online at https://portals.broadinstitute.org/single_cell/study/aging-mouse-brain ) provide a resource for the neuroscience community that will facilitate additional discoveries directed towards understanding and modifying the aging process.

PMID:
31551601
DOI:
10.1038/s41593-019-0491-3
[Indexed for MEDLINE]

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