دورية أكاديمية
أعرض في EDS

Single-nuclei transcriptome analysis of Huntington disease iPSC and mouse astrocytes implicates maturation and functional deficits.

التفاصيل البيبلوغرافية
العنوان: Single-nuclei transcriptome analysis of Huntington disease iPSC and mouse astrocytes implicates maturation and functional deficits.
المؤلفون: Reyes-Ortiz AM; Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92617, USA., Abud EM; Department of Neurobiology & Behavior, University of California, Irvine, Irvine, CA 92617, USA., Burns MS; Department of Neurobiology & Behavior, University of California, Irvine, Irvine, CA 92617, USA., Wu J; Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92617, USA., Hernandez SJ; Department of Neurobiology & Behavior, University of California, Irvine, Irvine, CA 92617, USA., McClure N; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92617, USA., Wang KQ; Department of Neurobiology & Behavior, University of California, Irvine, Irvine, CA 92617, USA., Schulz CJ; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92617, USA., Miramontes R; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92617, USA., Lau A; Department of Psychiatry & Human Behavior, University of California, Irvine, Irvine, CA 92617, USA., Michael N; Department of Neurobiology & Behavior, University of California, Irvine, Irvine, CA 92617, USA., Miyoshi E; Department of Neurobiology & Behavior, University of California, Irvine, Irvine, CA 92617, USA., Van Vactor D; Harvard Medical School, Department of Cell Biology, Boston, MA 02115, USA., Reidling JC; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92617, USA., Blurton-Jones M; Department of Neurobiology & Behavior, University of California, Irvine, Irvine, CA 92617, USA.; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92617, USA.; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92617, USA., Swarup V; Department of Neurobiology & Behavior, University of California, Irvine, Irvine, CA 92617, USA.; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92617, USA., Poon WW; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92617, USA., Lim RG; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92617, USA., Thompson LM; Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92617, USA.; Department of Neurobiology & Behavior, University of California, Irvine, Irvine, CA 92617, USA.; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92617, USA.; Department of Psychiatry & Human Behavior, University of California, Irvine, Irvine, CA 92617, USA.; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92617, USA.
المصدر: IScience [iScience] 2022 Dec 06; Vol. 26 (1), pp. 105732. Date of Electronic Publication: 2022 Dec 06 (Print Publication: 2023).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101724038 Publication Model: eCollection Cited Medium: Internet ISSN: 2589-0042 (Electronic) Linking ISSN: 25890042 NLM ISO Abbreviation: iScience Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Cambridge, MA] : Cell Press, [2018]-
مستخلص: Huntington disease (HD) is a neurodegenerative disorder caused by expanded CAG repeats in the huntingtin gene that alters cellular homeostasis, particularly in the striatum and cortex. Astrocyte signaling that establishes and maintains neuronal functions are often altered under pathological conditions. We performed single-nuclei RNA-sequencing on human HD patient-induced pluripotent stem cell (iPSC)-derived astrocytes and on striatal and cortical tissue from R6/2 HD mice to investigate high-resolution HD astrocyte cell state transitions. We observed altered maturation and glutamate signaling in HD human and mouse astrocytes. Human HD astrocytes also showed upregulated actin-mediated signaling, suggesting that some states may be cell-autonomous and human specific. In both species, astrogliogenesis transcription factors may drive HD astrocyte maturation deficits, which are supported by rescued climbing deficits in HD drosophila with NFIA knockdown. Thus, dysregulated HD astrocyte states may induce dysfunctional astrocytic properties, in part due to maturation deficits influenced by astrogliogenesis transcription factor dysregulation.
Competing Interests: The authors declare no competing interests. Some authors have additional affiliations as noted below: Andrea M. Reyes-Ortiz: Genentech, Inc., South San Francisco, California. Edsel M. Abud: Scripps Research Translational Institute, La Jolla, California and Division of Allergy, Asthma, and Immunology, Scripps Clinic, San Diego, California. Ryan G. Lim: Modulo Bio, Inc., San Diego, California. Wayne W. Poon: NeuCyte, Inc., Mountain View, California. Patent Pending: GENERATION AND APPLICATION OF FUNCTIONAL HUMAN ASTROCYTES FROM PLURIPOTENT STEM CELLS. Inventors: Edsel Abud, Wayne Poon.
(© 2022 The Authors.)
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معلومات مُعتمدة: S10 OD021718 United States OD NIH HHS; R35 NS116872 United States NS NINDS NIH HHS; S10 RR025496 United States RR NCRR NIH HHS; R21 NS123207 United States NS NINDS NIH HHS; R01 NS089076 United States NS NINDS NIH HHS; RF1 AG071683 United States AG NIA NIH HHS; T32 NS082174 United States NS NINDS NIH HHS; S10 OD010794 United States OD NIH HHS; P01 NS092525 United States NS NINDS NIH HHS; P30 CA062203 United States CA NCI NIH HHS; R01 AG071683 United States AG NIA NIH HHS
فهرسة مساهمة: Keywords: Neurology; Omics
تواريخ الأحداث: Date Created: 20230102 Latest Revision: 20240321
رمز التحديث: 20240321
مُعرف محوري في PubMed: PMC9800269
DOI: 10.1016/j.isci.2022.105732
PMID: 36590162
قاعدة البيانات: MEDLINE
الوصف
تدمد:2589-0042
DOI:10.1016/j.isci.2022.105732