دورية أكاديمية
أعرض في EDS

Transcriptional landscape of human microglia implicates age, sex, and APOE-related immunometabolic pathway perturbations.

التفاصيل البيبلوغرافية
العنوان: Transcriptional landscape of human microglia implicates age, sex, and APOE-related immunometabolic pathway perturbations.
المؤلفون: Patel T; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA., Carnwath TP; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA., Wang X; Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, Florida, USA., Allen M; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA., Lincoln SJ; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA., Lewis-Tuffin LJ; Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, USA., Quicksall ZS; Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, Florida, USA., Lin S; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA., Tutor-New FQ; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA., Ho CCG; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA., Min Y; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA., Malphrus KG; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA., Nguyen TT; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA., Martin E; Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida, USA., Garcia CA; Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida, USA., Alkharboosh RM; Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida, USA.; Neuroscience Graduate Program, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, Minnesota, USA.; Regenerative Sciences Training Program, Center for Regenerative Medicine, Mayo Clinic, Rochester, Minnesota, USA., Grewal S; Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida, USA., Chaichana K; Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida, USA., Wharen R; Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida, USA., Guerrero-Cazares H; Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida, USA., Quinones-Hinojosa A; Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida, USA., Ertekin-Taner N; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.; Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
المصدر: Aging cell [Aging Cell] 2022 May; Vol. 21 (5), pp. e13606. Date of Electronic Publication: 2022 Apr 06.
نوع المنشور: Journal Article; Meta-Analysis
اللغة: English
بيانات الدورية: Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101130839 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1474-9726 (Electronic) Linking ISSN: 14749718 NLM ISO Abbreviation: Aging Cell Subsets: MEDLINE
أسماء مطبوعة: Publication: Oxford, UK : Wiley-Blackwell
Original Publication: Oxford, UK : Blackwell Pub., c2002-
مواضيع طبية MeSH: Alzheimer Disease*/metabolism , Neurodegenerative Diseases*/genetics , Neurodegenerative Diseases*/metabolism, Apolipoproteins E/genetics ; Apolipoproteins E/metabolism ; Humans ; Microglia/metabolism ; Transcriptome/genetics
مستخلص: Microglia have fundamental roles in health and disease; however, effects of age, sex, and genetic factors on human microglia have not been fully explored. We applied bulk and single-cell approaches to comprehensively characterize human microglia transcriptomes and their associations with age, sex, and APOE. We identified a novel microglial signature, characterized its expression in bulk tissue and single-cell microglia transcriptomes. We discovered microglial co-expression network modules associated with age, sex, and APOE-ε4 that are enriched for lipid and carbohydrate metabolism genes. Integrated analyses of modules with single-cell transcriptomes revealed significant overlap between age-associated module genes and both pro-inflammatory and disease-associated microglial clusters. These modules and clusters harbor known neurodegenerative disease genes including APOE, PLCG2, and BIN1. Meta-analyses with published bulk and single-cell microglial datasets further supported our findings. Thus, these data represent a well-characterized human microglial transcriptome resource and highlight age, sex, and APOE-related microglial immunometabolism perturbations with potential relevance in neurodegeneration.
(© 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)
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معلومات مُعتمدة: U01 AG046152 United States AG NIA NIH HHS; P50 AG016574 United States AG NIA NIH HHS; R01 AG017917 United States AG NIA NIH HHS; RF1 AG051504 United States AG NIA NIH HHS; R01 NS080820 United States NS NINDS NIH HHS; RC2 AG036547 United States AG NIA NIH HHS; P30 AG062677 United States AG NIA NIH HHS; P01 AG017216 United States AG NIA NIH HHS; R01 AG018023 United States AG NIA NIH HHS; U01 AG061356 United States AG NIA NIH HHS; U01 AG032984 United States AG NIA NIH HHS; R01 AG030146 United States AG NIA NIH HHS; U01 AG046170 United States AG NIA NIH HHS; R01 AG036042 United States AG NIA NIH HHS; P30 AG010161 United States AG NIA NIH HHS; R01 AG061796 United States AG NIA NIH HHS; R01 AG032990 United States AG NIA NIH HHS; RF1 AG057473 United States AG NIA NIH HHS; U01 AG046139 United States AG NIA NIH HHS; P01 AG003949 United States AG NIA NIH HHS; U24 NS072026 United States NS NINDS NIH HHS; U01 AG046161 United States AG NIA NIH HHS; P30 AG019610 United States AG NIA NIH HHS; R01 AG048015 United States AG NIA NIH HHS; P50 AG025711 United States AG NIA NIH HHS; U01 AG006786 United States AG NIA NIH HHS; R01 AG036836 United States AG NIA NIH HHS; R01 AG015819 United States AG NIA NIH HHS
فهرسة مساهمة: Keywords: APOE; lipid metabolism; microglia; neurodegeneration; single cell; transcriptomics
المشرفين على المادة: 0 (Apolipoproteins E)
تواريخ الأحداث: Date Created: 20220407 Date Completed: 20220524 Latest Revision: 20240214
رمز التحديث: 20240214
مُعرف محوري في PubMed: PMC9124307
DOI: 10.1111/acel.13606
PMID: 35388616
قاعدة البيانات: MEDLINE
الوصف
تدمد:1474-9726
DOI:10.1111/acel.13606