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Title: A transcriptomic atlas of aged human microglia

Abstract

With a rapidly aging global human population, finding a cure for late onset neurodegenerative diseases has become an urgent enterprise. However, these efforts are hindered by the lack of understanding of what constitutes the phenotype of aged human microglia—the cell type that has been strongly implicated by genetic studies in the pathogenesis of age-related neurodegenerative disease. Here, we establish the set of genes that is preferentially expressed by microglia in the aged human brain. This HuMi_Aged gene set captures a unique phenotype, which we confirm at the protein level. Furthermore, we find this gene set to be enriched in susceptibility genes for Alzheimer’s disease and multiple sclerosis, to be increased with advancing age, and to be reduced by the protective APOEe2 haplotype. APOEe4 has no effect. These findings confirm the existence of an aging-related microglial phenotype in the aged human brain and its involvement in the pathological processes associated with brain aging.

Authors:
 [1]; ORCiD logo [2];  [3]; ORCiD logo [4];  [4];  [5]; ORCiD logo [6];  [6];  [4]; ORCiD logo [5];  [1];  [7];  [5];  [5];  [1]; ORCiD logo [6];  [8];  [8]; ORCiD logo [1];  [1]
  1. Columbia Univ. Medical Center, New York City, NY (United States); Broad Inst., Cambridge, MA (United States)
  2. Univ. of Sydney, NSW (Australia)
  3. Broad Inst., Cambridge, MA (United States); Massachusetts General Hospital, Boston, MA (United States)
  4. Broad Inst., Cambridge, MA (United States)
  5. Brigham and Women's Hospital (Harvard Medical School), Boston, MA (United States)
  6. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  7. Columbia Univ. Medical Center, New York City, NY (United States)
  8. Rush Univ. Medical Center, Chicago, IL (United States)
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1490325
Report Number(s):
PNNL-SA-134273
Journal ID: ISSN 2041-1723
Grant/Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 9; Journal Issue: 1; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

Olah, Marta, Patrick, Ellis, Villani, Alexandra-Chloe, Xu, Jishu, White, Charles C., Ryan, Katie J., Piehowski, Paul, Kapasi, Alifiya, Nejad, Parham, Cimpean, Maria, Connor, Sarah, Yung, Christina J., Frangieh, Michael, McHenry, Allison, Elyaman, Wassim, Petyuk, Vlad, Schneider, Julie A., Bennett, David A., De Jager, Philip L., and Bradshaw, Elizabeth M.. A transcriptomic atlas of aged human microglia. United States: N. p., 2018. Web. doi:10.1038/s41467-018-02926-5.
Olah, Marta, Patrick, Ellis, Villani, Alexandra-Chloe, Xu, Jishu, White, Charles C., Ryan, Katie J., Piehowski, Paul, Kapasi, Alifiya, Nejad, Parham, Cimpean, Maria, Connor, Sarah, Yung, Christina J., Frangieh, Michael, McHenry, Allison, Elyaman, Wassim, Petyuk, Vlad, Schneider, Julie A., Bennett, David A., De Jager, Philip L., & Bradshaw, Elizabeth M.. A transcriptomic atlas of aged human microglia. United States. doi:10.1038/s41467-018-02926-5.
Olah, Marta, Patrick, Ellis, Villani, Alexandra-Chloe, Xu, Jishu, White, Charles C., Ryan, Katie J., Piehowski, Paul, Kapasi, Alifiya, Nejad, Parham, Cimpean, Maria, Connor, Sarah, Yung, Christina J., Frangieh, Michael, McHenry, Allison, Elyaman, Wassim, Petyuk, Vlad, Schneider, Julie A., Bennett, David A., De Jager, Philip L., and Bradshaw, Elizabeth M.. Wed . "A transcriptomic atlas of aged human microglia". United States. doi:10.1038/s41467-018-02926-5. https://www.osti.gov/servlets/purl/1490325.
@article{osti_1490325,
title = {A transcriptomic atlas of aged human microglia},
author = {Olah, Marta and Patrick, Ellis and Villani, Alexandra-Chloe and Xu, Jishu and White, Charles C. and Ryan, Katie J. and Piehowski, Paul and Kapasi, Alifiya and Nejad, Parham and Cimpean, Maria and Connor, Sarah and Yung, Christina J. and Frangieh, Michael and McHenry, Allison and Elyaman, Wassim and Petyuk, Vlad and Schneider, Julie A. and Bennett, David A. and De Jager, Philip L. and Bradshaw, Elizabeth M.},
abstractNote = {With a rapidly aging global human population, finding a cure for late onset neurodegenerative diseases has become an urgent enterprise. However, these efforts are hindered by the lack of understanding of what constitutes the phenotype of aged human microglia—the cell type that has been strongly implicated by genetic studies in the pathogenesis of age-related neurodegenerative disease. Here, we establish the set of genes that is preferentially expressed by microglia in the aged human brain. This HuMi_Aged gene set captures a unique phenotype, which we confirm at the protein level. Furthermore, we find this gene set to be enriched in susceptibility genes for Alzheimer’s disease and multiple sclerosis, to be increased with advancing age, and to be reduced by the protective APOEe2 haplotype. APOEe4 has no effect. These findings confirm the existence of an aging-related microglial phenotype in the aged human brain and its involvement in the pathological processes associated with brain aging.},
doi = {10.1038/s41467-018-02926-5},
journal = {Nature Communications},
number = 1,
volume = 9,
place = {United States},
year = {Wed Feb 07 00:00:00 EST 2018},
month = {Wed Feb 07 00:00:00 EST 2018}
}

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Works referenced in this record:

Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles
journal, September 2005

  • Subramanian, A.; Tamayo, P.; Mootha, V. K.
  • Proceedings of the National Academy of Sciences, Vol. 102, Issue 43, p. 15545-15550
  • DOI: 10.1073/pnas.0506580102