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Single-nucleus RNA-seq identifies Huntington disease astrocyte states

Huntington Disease (HD) is an inherited movement disorder caused by expanded CAG repeats in the Huntingtin gene. We have used single nucleus RNASeq (snRNASeq) to uncover cellular phenotypes that change in the disease, investigating single cell gene expression in cingulate cortex of patients with HD...

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Autores principales: Al-Dalahmah, Osama, Sosunov, Alexander A., Shaik, A., Ofori, Kenneth, Liu, Yang, Vonsattel, Jean Paul, Adorjan, Istvan, Menon, Vilas, Goldman, James E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029580/
https://www.ncbi.nlm.nih.gov/pubmed/32070434
http://dx.doi.org/10.1186/s40478-020-0880-6
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author Al-Dalahmah, Osama
Sosunov, Alexander A.
Shaik, A.
Ofori, Kenneth
Liu, Yang
Vonsattel, Jean Paul
Adorjan, Istvan
Menon, Vilas
Goldman, James E.
author_facet Al-Dalahmah, Osama
Sosunov, Alexander A.
Shaik, A.
Ofori, Kenneth
Liu, Yang
Vonsattel, Jean Paul
Adorjan, Istvan
Menon, Vilas
Goldman, James E.
author_sort Al-Dalahmah, Osama
collection PubMed
description Huntington Disease (HD) is an inherited movement disorder caused by expanded CAG repeats in the Huntingtin gene. We have used single nucleus RNASeq (snRNASeq) to uncover cellular phenotypes that change in the disease, investigating single cell gene expression in cingulate cortex of patients with HD and comparing the gene expression to that of patients with no neurological disease. In this study, we focused on astrocytes, although we found significant gene expression differences in neurons, oligodendrocytes, and microglia as well. In particular, the gene expression profiles of astrocytes in HD showed multiple signatures, varying in phenotype from cells that had markedly upregulated metallothionein and heat shock genes, but had not completely lost the expression of genes associated with normal protoplasmic astrocytes, to astrocytes that had substantially upregulated glial fibrillary acidic protein (GFAP) and had lost expression of many normal protoplasmic astrocyte genes as well as metallothionein genes. When compared to astrocytes in control samples, astrocyte signatures in HD also showed downregulated expression of a number of genes, including several associated with protoplasmic astrocyte function and lipid synthesis. Thus, HD astrocytes appeared in variable transcriptional phenotypes, and could be divided into several different “states”, defined by patterns of gene expression. Ultimately, this study begins to fill the knowledge gap of single cell gene expression in HD and provide a more detailed understanding of the variation in changes in gene expression during astrocyte “reactions” to the disease.
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spelling pubmed-70295802020-02-25 Single-nucleus RNA-seq identifies Huntington disease astrocyte states Al-Dalahmah, Osama Sosunov, Alexander A. Shaik, A. Ofori, Kenneth Liu, Yang Vonsattel, Jean Paul Adorjan, Istvan Menon, Vilas Goldman, James E. Acta Neuropathol Commun Research Huntington Disease (HD) is an inherited movement disorder caused by expanded CAG repeats in the Huntingtin gene. We have used single nucleus RNASeq (snRNASeq) to uncover cellular phenotypes that change in the disease, investigating single cell gene expression in cingulate cortex of patients with HD and comparing the gene expression to that of patients with no neurological disease. In this study, we focused on astrocytes, although we found significant gene expression differences in neurons, oligodendrocytes, and microglia as well. In particular, the gene expression profiles of astrocytes in HD showed multiple signatures, varying in phenotype from cells that had markedly upregulated metallothionein and heat shock genes, but had not completely lost the expression of genes associated with normal protoplasmic astrocytes, to astrocytes that had substantially upregulated glial fibrillary acidic protein (GFAP) and had lost expression of many normal protoplasmic astrocyte genes as well as metallothionein genes. When compared to astrocytes in control samples, astrocyte signatures in HD also showed downregulated expression of a number of genes, including several associated with protoplasmic astrocyte function and lipid synthesis. Thus, HD astrocytes appeared in variable transcriptional phenotypes, and could be divided into several different “states”, defined by patterns of gene expression. Ultimately, this study begins to fill the knowledge gap of single cell gene expression in HD and provide a more detailed understanding of the variation in changes in gene expression during astrocyte “reactions” to the disease. BioMed Central 2020-02-18 /pmc/articles/PMC7029580/ /pubmed/32070434 http://dx.doi.org/10.1186/s40478-020-0880-6 Text en © The Author(s). 2020 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Al-Dalahmah, Osama
Sosunov, Alexander A.
Shaik, A.
Ofori, Kenneth
Liu, Yang
Vonsattel, Jean Paul
Adorjan, Istvan
Menon, Vilas
Goldman, James E.
Single-nucleus RNA-seq identifies Huntington disease astrocyte states
title Single-nucleus RNA-seq identifies Huntington disease astrocyte states
title_full Single-nucleus RNA-seq identifies Huntington disease astrocyte states
title_fullStr Single-nucleus RNA-seq identifies Huntington disease astrocyte states
title_full_unstemmed Single-nucleus RNA-seq identifies Huntington disease astrocyte states
title_short Single-nucleus RNA-seq identifies Huntington disease astrocyte states
title_sort single-nucleus rna-seq identifies huntington disease astrocyte states
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029580/
https://www.ncbi.nlm.nih.gov/pubmed/32070434
http://dx.doi.org/10.1186/s40478-020-0880-6
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