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A map of transcriptional heterogeneity and regulatory variation in human microglia.
Young, Adam M H; Kumasaka, Natsuhiko; Calvert, Fiona; Hammond, Timothy R; Knights, Andrew; Panousis, Nikolaos; Park, Jun Sung; Schwartzentruber, Jeremy; Liu, Jimmy; Kundu, Kousik; Segel, Michael; Murphy, Natalia A; McMurran, Christopher E; Bulstrode, Harry; Correia, Jason; Budohoski, Karol P; Joannides, Alexis; Guilfoyle, Mathew R; Trivedi, Rikin; Kirollos, Ramez; Morris, Robert; Garnett, Matthew R; Timofeev, Ivan; Jalloh, Ibrahim; Holland, Katherine; Mannion, Richard; Mair, Richard; Watts, Colin; Price, Stephen J; Kirkpatrick, Peter J; Santarius, Thomas; Mountjoy, Edward; Ghoussaini, Maya; Soranzo, Nicole; Bayraktar, Omer A; Stevens, Beth; Hutchinson, Peter J; Franklin, Robin J M; Gaffney, Daniel J.
Affiliation
  • Young AMH; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
  • Kumasaka N; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
  • Calvert F; Division of Neurosurgery, Department of Clinical Neurosciences, Cambridge University Hospitals, Cambridge, UK.
  • Hammond TR; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
  • Knights A; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
  • Panousis N; FM Kirby Neurobiology Center, Boston Children's Hospital Harvard University, Boston, MA, USA.
  • Park JS; Howard Hughes Medical Institute, Broad Institute of Harvard and MIT, Boston, MA, USA.
  • Schwartzentruber J; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
  • Liu J; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
  • Kundu K; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
  • Segel M; EMBL-EBI, Wellcome Genome Campus, Hinxton, UK.
  • Murphy NA; Biogen, Cambridge, MA, USA.
  • McMurran CE; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
  • Bulstrode H; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
  • Correia J; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
  • Budohoski KP; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
  • Joannides A; Division of Neurosurgery, Department of Clinical Neurosciences, Cambridge University Hospitals, Cambridge, UK.
  • Guilfoyle MR; Division of Neurosurgery, Department of Clinical Neurosciences, Cambridge University Hospitals, Cambridge, UK.
  • Trivedi R; Division of Neurosurgery, Department of Clinical Neurosciences, Cambridge University Hospitals, Cambridge, UK.
  • Kirollos R; Division of Neurosurgery, Department of Clinical Neurosciences, Cambridge University Hospitals, Cambridge, UK.
  • Morris R; Division of Neurosurgery, Department of Clinical Neurosciences, Cambridge University Hospitals, Cambridge, UK.
  • Garnett MR; Division of Neurosurgery, Department of Clinical Neurosciences, Cambridge University Hospitals, Cambridge, UK.
  • Timofeev I; Division of Neurosurgery, Department of Clinical Neurosciences, Cambridge University Hospitals, Cambridge, UK.
  • Jalloh I; Division of Neurosurgery, Department of Clinical Neurosciences, Cambridge University Hospitals, Cambridge, UK.
  • Holland K; Division of Neurosurgery, Department of Clinical Neurosciences, Cambridge University Hospitals, Cambridge, UK.
  • Mannion R; Division of Neurosurgery, Department of Clinical Neurosciences, Cambridge University Hospitals, Cambridge, UK.
  • Mair R; Division of Neurosurgery, Department of Clinical Neurosciences, Cambridge University Hospitals, Cambridge, UK.
  • Watts C; Division of Neurosurgery, Department of Clinical Neurosciences, Cambridge University Hospitals, Cambridge, UK.
  • Price SJ; Division of Neurosurgery, Department of Clinical Neurosciences, Cambridge University Hospitals, Cambridge, UK.
  • Kirkpatrick PJ; Division of Neurosurgery, Department of Clinical Neurosciences, Cambridge University Hospitals, Cambridge, UK.
  • Santarius T; Division of Neurosurgery, Department of Clinical Neurosciences, Cambridge University Hospitals, Cambridge, UK.
  • Mountjoy E; Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, Birmingham, UK.
  • Ghoussaini M; Division of Neurosurgery, Department of Clinical Neurosciences, Cambridge University Hospitals, Cambridge, UK.
  • Soranzo N; Division of Neurosurgery, Department of Clinical Neurosciences, Cambridge University Hospitals, Cambridge, UK.
  • Bayraktar OA; Division of Neurosurgery, Department of Clinical Neurosciences, Cambridge University Hospitals, Cambridge, UK.
  • Stevens B; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
  • Hutchinson PJ; Open Targets, Wellcome Genome Campus, Hinxton, UK.
  • Franklin RJM; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
  • Gaffney DJ; Open Targets, Wellcome Genome Campus, Hinxton, UK.
Nat Genet ; 53(6): 861-868, 2021 06.
Article in En | MEDLINE | ID: mdl-34083789
ABSTRACT
Microglia, the tissue-resident macrophages of the central nervous system (CNS), play critical roles in immune defense, development and homeostasis. However, isolating microglia from humans in large numbers is challenging. Here, we profiled gene expression variation in primary human microglia isolated from 141 patients undergoing neurosurgery. Using single-cell and bulk RNA sequencing, we identify how age, sex and clinical pathology influence microglia gene expression and which genetic variants have microglia-specific functions using expression quantitative trait loci (eQTL) mapping. We follow up one of our findings using a human induced pluripotent stem cell-based macrophage model to fine-map a candidate causal variant for Alzheimer's disease at the BIN1 locus. Our study provides a population-scale transcriptional map of a critically important cell for human CNS development and disease.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Transcription, Genetic / Gene Expression Regulation / Microglia Type of study: Prognostic_studies Limits: Humans Language: En Journal: Nat Genet Journal subject: GENETICA MEDICA Year: 2021 Document type: Article Affiliation country:
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Transcription, Genetic / Gene Expression Regulation / Microglia Type of study: Prognostic_studies Limits: Humans Language: En Journal: Nat Genet Journal subject: GENETICA MEDICA Year: 2021 Document type: Article Affiliation country: