Multi-modal Single-Cell Analysis Reveals Brain Immune Landscape Plasticity during Aging and Gut Microbiota Dysbiosis

Samantha M. Golomb, Ian H. Guldner, Anqi Zhao, Qingfei Wang, Bhavana Palakurthi, Emilija A. Aleksandrovic, Jacqueline A. Lopez, Shaun W. Lee, Kai Yang, Siyuan Zhang

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Phenotypic and functional plasticity of brain immune cells contribute to brain tissue homeostasis and disease. Immune cell plasticity is profoundly influenced by tissue microenvironment cues and systemic factors. Aging and gut microbiota dysbiosis that reshape brain immune cell plasticity and homeostasis has not been fully delineated. Using Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq), we analyze compositional and transcriptional changes of the brain immune landscape in response to aging and gut dysbiosis. Discordance between canonical surface-marker-defined immune cell types and their transcriptomes suggest transcriptional plasticity among immune cells. Ly6C+ monocytes predominate a pro-inflammatory signature in the aged brain, while innate lymphoid cells (ILCs) shift toward an ILC2-like profile. Aging increases ILC-like cells expressing a T memory stemness (Tscm) signature, which is reduced through antibiotics-induced gut dysbiosis. Systemic changes due to aging and gut dysbiosis increase propensity for neuroinflammation, providing insights into gut dysbiosis in age-related neurological diseases.

Original languageEnglish (US)
Article number108438
JournalCell Reports
Volume33
Issue number9
DOIs
StatePublished - Dec 1 2020
Externally publishedYes

Keywords

  • aging
  • brain
  • brain immunity
  • CITE-seq
  • CNS
  • dysbiosis
  • gut microbiota
  • single-cell sequencing

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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