دورية أكاديمية
أعرض في EDS

Identification of astrocyte regulators by nucleic acid cytometry.

التفاصيل البيبلوغرافية
العنوان: Identification of astrocyte regulators by nucleic acid cytometry.
المؤلفون: Clark IC; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Department of Bioengineering and Therapeutic Sciences, School of Pharmacy, University of California San Francisco, San Francisco, CA, USA.; Department of Bioengineering, College of Engineering, California Institute for Quantitative Biosciences, QB3, University of California Berkeley, Berkeley, CA, USA., Wheeler MA; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Lee HG; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Li Z; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Sanmarco LM; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Thaploo S; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Polonio CM; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Shin SW; Department of Bioengineering, College of Engineering, California Institute for Quantitative Biosciences, QB3, University of California Berkeley, Berkeley, CA, USA., Scalisi G; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Henry AR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Rone JM; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Giovannoni F; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Charabati M; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Akl CF; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Aleman DM; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Zandee SEJ; Neuroimmunology Research Lab, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada., Prat A; Neuroimmunology Research Lab, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada., Douek DC; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Boritz EA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Quintana FJ; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. fquintana@rics.bwh.harvard.edu.; Broad Institute of MIT and Harvard, Cambridge, MA, USA. fquintana@rics.bwh.harvard.edu., Abate AR; Department of Bioengineering and Therapeutic Sciences, School of Pharmacy, University of California San Francisco, San Francisco, CA, USA. adam@abatelab.org.
المصدر: Nature [Nature] 2023 Feb; Vol. 614 (7947), pp. 326-333. Date of Electronic Publication: 2023 Jan 04.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE
أسماء مطبوعة: Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.
مواضيع طبية MeSH: Astrocytes*/metabolism , Astrocytes*/pathology , Encephalomyelitis, Autoimmune, Experimental* , Multiple Sclerosis*/pathology , Microfluidics*/methods , Single-Cell Gene Expression Analysis*/methods , Nucleic Acids*/analysis, Animals ; Humans ; Mice ; Gene Expression Regulation ; Mice, Knockout ; Gene Editing
مستخلص: Multiple sclerosis is a chronic inflammatory disease of the central nervous system 1 . Astrocytes are heterogeneous glial cells that are resident in the central nervous system and participate in the pathogenesis of multiple sclerosis and its model experimental autoimmune encephalomyelitis 2,3 . However, few unique surface markers are available for the isolation of astrocyte subsets, preventing their analysis and the identification of candidate therapeutic targets; these limitations are further amplified by the rarity of pathogenic astrocytes. Here, to address these challenges, we developed focused interrogation of cells by nucleic acid detection and sequencing (FIND-seq), a high-throughput microfluidic cytometry method that combines encapsulation of cells in droplets, PCR-based detection of target nucleic acids and droplet sorting to enable in-depth transcriptomic analyses of cells of interest at single-cell resolution. We applied FIND-seq to study the regulation of astrocytes characterized by the splicing-driven activation of the transcription factor XBP1, which promotes disease pathology in multiple sclerosis and experimental autoimmune encephalomyelitis 4 . Using FIND-seq in combination with conditional-knockout mice, in vivo CRISPR-Cas9-driven genetic perturbation studies and bulk and single-cell RNA sequencing analyses of samples from mouse experimental autoimmune encephalomyelitis and humans with multiple sclerosis, we identified a new role for the nuclear receptor NR3C2 and its corepressor NCOR2 in limiting XBP1-driven pathogenic astrocyte responses. In summary, we used FIND-seq to identify a therapeutically targetable mechanism that limits XBP1-driven pathogenic astrocyte responses. FIND-seq enables the investigation of previously inaccessible cells, including rare cell subsets defined by unique gene expression signatures or other nucleic acid markers.
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
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معلومات مُعتمدة: R01 MH130458 United States MH NIMH NIH HHS; R01 ES032323 United States ES NIEHS NIH HHS; K99 NS114111 United States NS NINDS NIH HHS; R01 AI126880 United States AI NIAID NIH HHS; DP2 AI154435 United States AI NIAID NIH HHS; F32 NS101790 United States NS NINDS NIH HHS; United Kingdom WT_ Wellcome Trust; U01 AI129206 United States AI NIAID NIH HHS; R00 NS114111 United States NS NINDS NIH HHS; K22 AI152644 United States AI NIAID NIH HHS; R01 ES025530 United States ES NIEHS NIH HHS; R01 AI149699 United States AI NIAID NIH HHS; R21 NS087867 United States NS NINDS NIH HHS; UM1 AI126611 United States AI NIAID NIH HHS; R01 NS129778 United States NS NINDS NIH HHS
المشرفين على المادة: 0 (Xbp1 protein, mouse)
0 (Nucleic Acids)
0 (NR3C2 protein, human)
0 (NCOR2 protein, human)
0 (XBP1 protein, human)
0 (Nr3c2 protein, mouse)
0 (Ncor2 protein, mouse)
تواريخ الأحداث: Date Created: 20230104 Date Completed: 20230217 Latest Revision: 20240312
رمز التحديث: 20240312
مُعرف محوري في PubMed: PMC9980163
DOI: 10.1038/s41586-022-05613-0
PMID: 36599367
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-4687
DOI:10.1038/s41586-022-05613-0