دورية أكاديمية
A map of transcriptional heterogeneity and regulatory variation in human microglia.
| العنوان: | A map of transcriptional heterogeneity and regulatory variation in human microglia. |
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| المؤلفون: | Young AMH; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.; Division of Neurosurgery, Department of Clinical Neurosciences, Cambridge University Hospitals, Cambridge, UK., Kumasaka N; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK., Calvert F; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK., Hammond TR; FM Kirby Neurobiology Center, Boston Children's Hospital Harvard University, Boston, MA, USA.; Howard Hughes Medical Institute, Broad Institute of Harvard and MIT, Boston, MA, USA., Knights A; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK., Panousis N; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK., Park JS; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK., Schwartzentruber J; EMBL-EBI, Wellcome Genome Campus, Hinxton, UK., Liu J; Biogen, Cambridge, MA, USA., Kundu K; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK., Segel M; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK., Murphy NA; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK., McMurran CE; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK., Bulstrode H; Division of Neurosurgery, Department of Clinical Neurosciences, Cambridge University Hospitals, Cambridge, UK., Correia J; Division of Neurosurgery, Department of Clinical Neurosciences, Cambridge University Hospitals, Cambridge, UK., Budohoski KP; Division of Neurosurgery, Department of Clinical Neurosciences, Cambridge University Hospitals, 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.; Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, Birmingham, 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; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.; Open Targets, Wellcome Genome Campus, Hinxton, UK., Ghoussaini M; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.; Open Targets, Wellcome Genome Campus, Hinxton, UK., Soranzo N; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK., Bayraktar OA; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK., Stevens B; FM Kirby Neurobiology Center, Boston Children's Hospital Harvard University, Boston, MA, USA.; Howard Hughes Medical Institute, Broad Institute of Harvard and MIT, Boston, MA, USA., Hutchinson PJ; Division of Neurosurgery, Department of Clinical Neurosciences, Cambridge University Hospitals, Cambridge, UK., Franklin RJM; Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK. rjf1000@cam.ac.uk., Gaffney DJ; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK. dg13@sanger.ac.uk. |
| المصدر: | Nature genetics [Nat Genet] 2021 Jun; Vol. 53 (6), pp. 861-868. Date of Electronic Publication: 2021 Jun 03. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Pub. Co Country of Publication: United States NLM ID: 9216904 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-1718 (Electronic) Linking ISSN: 10614036 NLM ISO Abbreviation: Nat Genet Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York, NY : Nature Pub. Co., c1992- |
| مواضيع طبية MeSH: | Gene Expression Regulation* , Transcription, Genetic*, Microglia/*metabolism, Alzheimer Disease/genetics ; Humans ; Models, Genetic ; Quantitative Trait Loci/genetics ; Sequence Analysis, RNA ; Single-Cell Analysis |
| مستخلص: | 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. |
| التعليقات: | Comment in: Nat Genet. 2021 Jun;53(6):766-767. (PMID: 34083790) |
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| معلومات مُعتمدة: | MC_PC_17230 United Kingdom MRC_ Medical Research Council; RRZD/029 United Kingdom WT_ Wellcome Trust; United States HHMI Howard Hughes Medical Institute; 206194 United Kingdom WT_ Wellcome Trust; United Kingdom WT_ Wellcome Trust; 203151 United Kingdom WT_ Wellcome Trust |
| تواريخ الأحداث: | Date Created: 20210604 Date Completed: 20210720 Latest Revision: 20230203 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC7610960 |
| DOI: | 10.1038/s41588-021-00875-2 |
| PMID: | 34083789 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1546-1718 |
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| DOI: | 10.1038/s41588-021-00875-2 |