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Single-cell transcriptomics of the aged mouse brain reveals convergent, divergent and unique aging signatures

View ORCID ProfileMethodios Ximerakis, View ORCID ProfileScott L. Lipnick, View ORCID ProfileSean K. Simmons, View ORCID ProfileXian Adiconis, View ORCID ProfileBrendan T. Innes, View ORCID ProfileDanielle Dionne, View ORCID ProfileLan Nguyen, View ORCID ProfileBrittany A. Mayweather, View ORCID ProfileCeren Ozek, View ORCID ProfileZachary Niziolek, View ORCID ProfileVincent L. Butty, View ORCID ProfileRuth Isserlin, View ORCID ProfileSean M. Buchanan, View ORCID ProfileStuart R. Levine, View ORCID ProfileAviv Regev, View ORCID ProfileGary D Bader, View ORCID ProfileJoshua Z. Levin, View ORCID ProfileLee L. Rubin
doi: https://doi.org/10.1101/440032
Methodios Ximerakis
1Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA
2Harvard Stem Cell Institute, Cambridge, MA 02138, USA
3Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
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Scott L. Lipnick
1Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA
2Harvard Stem Cell Institute, Cambridge, MA 02138, USA
3Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA
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Sean K. Simmons
3Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
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Xian Adiconis
3Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
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Brendan T. Innes
5The Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada
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Danielle Dionne
3Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
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Lan Nguyen
3Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
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Brittany A. Mayweather
1Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA
2Harvard Stem Cell Institute, Cambridge, MA 02138, USA
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Ceren Ozek
1Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA
2Harvard Stem Cell Institute, Cambridge, MA 02138, USA
3Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
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Zachary Niziolek
6Bauer Core, FAS Division of Science, Harvard University, Cambridge, MA 02138, USA
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  • ORCID record for Zachary Niziolek
Vincent L. Butty
7BioMicro Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
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Ruth Isserlin
5The Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada
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  • ORCID record for Ruth Isserlin
Sean M. Buchanan
1Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA
2Harvard Stem Cell Institute, Cambridge, MA 02138, USA
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Stuart R. Levine
7BioMicro Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
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Aviv Regev
3Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
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Gary D Bader
5The Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada
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Joshua Z. Levin
3Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
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Lee L. Rubin
1Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA
2Harvard Stem Cell Institute, Cambridge, MA 02138, USA
3Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
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  • For correspondence: lee_rubin@harvard.edu
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Abstract

The mammalian brain is complex, with multiple cell types performing a variety of diverse functions, but exactly how the brain is affected with aging remains largely unknown. Here we performed a single-cell transcriptomic analysis of young and old mouse brains. We provide a comprehensive dataset 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. Thus, our data reveals that aging, rather than inducing a universal program drives a distinct transcriptional course in each cell population. These data provide an important resource for the aging community and highlight key molecular processes, including ribosomal biogenesis, underlying aging. We believe that this large-scale dataset, which is publicly accessible online (aging-mouse-brain), will facilitate additional discoveries directed towards understanding and modifying the aging process.

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Posted October 11, 2018.
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Single-cell transcriptomics of the aged mouse brain reveals convergent, divergent and unique aging signatures
Methodios Ximerakis, Scott L. Lipnick, Sean K. Simmons, Xian Adiconis, Brendan T. Innes, Danielle Dionne, Lan Nguyen, Brittany A. Mayweather, Ceren Ozek, Zachary Niziolek, Vincent L. Butty, Ruth Isserlin, Sean M. Buchanan, Stuart R. Levine, Aviv Regev, Gary D Bader, Joshua Z. Levin, Lee L. Rubin
bioRxiv 440032; doi: https://doi.org/10.1101/440032
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Single-cell transcriptomics of the aged mouse brain reveals convergent, divergent and unique aging signatures
Methodios Ximerakis, Scott L. Lipnick, Sean K. Simmons, Xian Adiconis, Brendan T. Innes, Danielle Dionne, Lan Nguyen, Brittany A. Mayweather, Ceren Ozek, Zachary Niziolek, Vincent L. Butty, Ruth Isserlin, Sean M. Buchanan, Stuart R. Levine, Aviv Regev, Gary D Bader, Joshua Z. Levin, Lee L. Rubin
bioRxiv 440032; doi: https://doi.org/10.1101/440032

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