Single-cell transcriptomic profiling of the aging mouse brain

Methodios Ximerakis^#^{1

2

3}, Scott L Lipnick^#^{4

5

6

7}, Brendan T Innes⁸, Sean K Simmons⁶, Xian Adiconis⁶, Danielle Dionne⁶, Brittany A Mayweather^{4

5}, Lan Nguyen⁶, Zachary Niziolek⁹, Ceren Ozek^{4

5}, Vincent L Butty¹⁰, Ruth Isserlin⁸, Sean M Buchanan^{4

5}, Stuart S Levine¹⁰, Aviv Regev⁶, Gary D Bader⁸, Joshua Z Levin⁶, Lee L Rubin^{11

12

13}

Affiliations

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.

^# Contributed equally.

PMID: 31551601
DOI: 10.1038/s41593-019-0491-3

Single-cell transcriptomic profiling of the aging mouse brain

Methodios Ximerakis et al. Nat Neurosci. 2019 Oct.

. 2019 Oct;22(10):1696-1708.

doi: 10.1038/s41593-019-0491-3. Epub 2019 Sep 24.

Authors

Affiliations

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.

^# Contributed equally.

PMID: 31551601
DOI: 10.1038/s41593-019-0491-3

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.

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References

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Single-cell transcriptomic profiling of the aging mouse brain

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Single-cell transcriptomic profiling of the aging mouse brain

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