@article{6d67c4fffff24af7bbb1534ec1a4de30,
title = "Multi-modal Single-Cell Analysis Reveals Brain Immune Landscape Plasticity during Aging and Gut Microbiota Dysbiosis",
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.",
keywords = "CITE-seq, CNS, aging, brain, brain immunity, dysbiosis, gut microbiota, single-cell sequencing",
author = "Golomb, {Samantha M.} and Guldner, {Ian H.} and Anqi Zhao and Qingfei Wang and Bhavana Palakurthi and Aleksandrovic, {Emilija A.} and Lopez, {Jacqueline A.} and Lee, {Shaun W.} and Kai Yang and Siyuan Zhang",
note = "Funding Information: This work was partially funded by NIH R01 CA194697-01 (S.Z.), NIH R01 CA222405 - 01A1 (S.Z.), the University of Notre Dame CRND Catalyst Award (S.Z.), and the Walther Cancer Foundation Harper Cancer Research Institute Award (S.M.G.). We acknowledge and thank the Dee Family endowment (S.Z.) and are additionally grateful for the technical support of the following core facilities: Notre Dame Genomics and Bioinformatics Core Facility, Notre Dame Freimann Life Sciences Center, Indiana University School of Medicine Center for Medical Genomics, and Indiana University Simon Cancer Center CTSI Center for Medical Genomics Core Facility. Funding Information: This work was partially funded by NIH R01 CA194697-01 (S.Z.), NIH R01 CA222405 - 01A1 (S.Z.), the University of Notre Dame CRND Catalyst Award (S.Z.), and the Walther Cancer Foundation Harper Cancer Research Institute Award (S.M.G.). We acknowledge and thank the Dee Family endowment (S.Z.) and are additionally grateful for the technical support of the following core facilities: Notre Dame Genomics and Bioinformatics Core Facility, Notre Dame Freimann Life Sciences Center, Indiana University School of Medicine Center for Medical Genomics, and Indiana University Simon Cancer Center CTSI Center for Medical Genomics Core Facility. S.M.G. I.H.G. and S.Z. conceived the original hypothesis and designed experiments. S.M.G. I.H.G. Q.W. B.P. E.A.A. J.A.L. and S.Z. performed experiments. S.M.G. I.H.G. A.Z. and S.Z. analyzed data. K.Y. and S.W.L. contributed critical intellectual guidance to this study. S.M.G. I.H.G. and S.Z. wrote and revised the manuscript. S.Z. supervised the study. All authors reviewed the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2020",
month = dec,
day = "1",
doi = "10.1016/j.celrep.2020.108438",
language = "English (US)",
volume = "33",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "9",
}