Cell-intrinsic glial pathology is conserved across human and murine models of Huntington's disease

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Cell-intrinsic glial pathology is conserved across human and murine models of Huntington's disease. / Benraiss, Abdellatif; Mariani, John N.; Osipovitch, Mikhail; Cornwell, Adam; Windrem, Martha S.; Villanueva, Carlos Benitez; Chandler-Militello, Devin; Goldman, Steven A.

In: Cell Reports, Vol. 36, No. 1, 109308, 2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Benraiss, A, Mariani, JN, Osipovitch, M, Cornwell, A, Windrem, MS, Villanueva, CB, Chandler-Militello, D & Goldman, SA 2021, 'Cell-intrinsic glial pathology is conserved across human and murine models of Huntington's disease', Cell Reports, vol. 36, no. 1, 109308. https://doi.org/10.1016/j.celrep.2021.109308

APA

Benraiss, A., Mariani, J. N., Osipovitch, M., Cornwell, A., Windrem, M. S., Villanueva, C. B., Chandler-Militello, D., & Goldman, S. A. (2021). Cell-intrinsic glial pathology is conserved across human and murine models of Huntington's disease. Cell Reports, 36(1), [109308]. https://doi.org/10.1016/j.celrep.2021.109308

Vancouver

Benraiss A, Mariani JN, Osipovitch M, Cornwell A, Windrem MS, Villanueva CB et al. Cell-intrinsic glial pathology is conserved across human and murine models of Huntington's disease. Cell Reports. 2021;36(1). 109308. https://doi.org/10.1016/j.celrep.2021.109308

Author

Benraiss, Abdellatif ; Mariani, John N. ; Osipovitch, Mikhail ; Cornwell, Adam ; Windrem, Martha S. ; Villanueva, Carlos Benitez ; Chandler-Militello, Devin ; Goldman, Steven A. / Cell-intrinsic glial pathology is conserved across human and murine models of Huntington's disease. In: Cell Reports. 2021 ; Vol. 36, No. 1.

Bibtex

@article{c3ca9d6a32a342188682ce9366a925d3,
title = "Cell-intrinsic glial pathology is conserved across human and murine models of Huntington's disease",
abstract = "Glial pathology is a causal contributor to the striatal neuronal dysfunction of Huntington's disease (HD). We investigate mutant HTT-associated changes in gene expression by mouse and human striatal astrocytes, as well as in mouse microglia, to identify commonalities in glial pathobiology across species and models. Mouse striatal astrocytes are fluorescence-activated cell sorted (FACS) from R6/2 and zQ175 mice, which respectively express exon1-only or full-length mHTT, and human astrocytes are generated either from human embryonic stem cells (hESCs) expressing full-length mHTT or from fetal striatal astrocytes transduced with exon1-only mHTT. Comparison of differential gene expression across these conditions, all with respect to normal HTT controls, reveals cell-type-specific changes in transcription common to both species, yet with differences that distinguish glia expressing truncated mHTT versus full-length mHTT. These data indicate that the differential gene expression of glia expressing truncated mHTT may differ from that of cells expressing full-length mHTT, while identifying a conserved set of dysregulated pathways in HD glia.",
keywords = "MUTANT HUNTINGTIN, GENE-EXPRESSION, TRANSCRIPTIONAL PROFILES, CHOLESTEROL-BIOSYNTHESIS, DECREASED EXPRESSION, PROGENITOR CELLS, MOUSE MODEL, CAG REPEAT, MICROGLIA, ASTROCYTES",
author = "Abdellatif Benraiss and Mariani, {John N.} and Mikhail Osipovitch and Adam Cornwell and Windrem, {Martha S.} and Villanueva, {Carlos Benitez} and Devin Chandler-Militello and Goldman, {Steven A.}",
year = "2021",
doi = "10.1016/j.celrep.2021.109308",
language = "English",
volume = "36",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "1",

}

RIS

TY - JOUR

T1 - Cell-intrinsic glial pathology is conserved across human and murine models of Huntington's disease

AU - Benraiss, Abdellatif

AU - Mariani, John N.

AU - Osipovitch, Mikhail

AU - Cornwell, Adam

AU - Windrem, Martha S.

AU - Villanueva, Carlos Benitez

AU - Chandler-Militello, Devin

AU - Goldman, Steven A.

PY - 2021

Y1 - 2021

N2 - Glial pathology is a causal contributor to the striatal neuronal dysfunction of Huntington's disease (HD). We investigate mutant HTT-associated changes in gene expression by mouse and human striatal astrocytes, as well as in mouse microglia, to identify commonalities in glial pathobiology across species and models. Mouse striatal astrocytes are fluorescence-activated cell sorted (FACS) from R6/2 and zQ175 mice, which respectively express exon1-only or full-length mHTT, and human astrocytes are generated either from human embryonic stem cells (hESCs) expressing full-length mHTT or from fetal striatal astrocytes transduced with exon1-only mHTT. Comparison of differential gene expression across these conditions, all with respect to normal HTT controls, reveals cell-type-specific changes in transcription common to both species, yet with differences that distinguish glia expressing truncated mHTT versus full-length mHTT. These data indicate that the differential gene expression of glia expressing truncated mHTT may differ from that of cells expressing full-length mHTT, while identifying a conserved set of dysregulated pathways in HD glia.

AB - Glial pathology is a causal contributor to the striatal neuronal dysfunction of Huntington's disease (HD). We investigate mutant HTT-associated changes in gene expression by mouse and human striatal astrocytes, as well as in mouse microglia, to identify commonalities in glial pathobiology across species and models. Mouse striatal astrocytes are fluorescence-activated cell sorted (FACS) from R6/2 and zQ175 mice, which respectively express exon1-only or full-length mHTT, and human astrocytes are generated either from human embryonic stem cells (hESCs) expressing full-length mHTT or from fetal striatal astrocytes transduced with exon1-only mHTT. Comparison of differential gene expression across these conditions, all with respect to normal HTT controls, reveals cell-type-specific changes in transcription common to both species, yet with differences that distinguish glia expressing truncated mHTT versus full-length mHTT. These data indicate that the differential gene expression of glia expressing truncated mHTT may differ from that of cells expressing full-length mHTT, while identifying a conserved set of dysregulated pathways in HD glia.

KW - MUTANT HUNTINGTIN

KW - GENE-EXPRESSION

KW - TRANSCRIPTIONAL PROFILES

KW - CHOLESTEROL-BIOSYNTHESIS

KW - DECREASED EXPRESSION

KW - PROGENITOR CELLS

KW - MOUSE MODEL

KW - CAG REPEAT

KW - MICROGLIA

KW - ASTROCYTES

U2 - 10.1016/j.celrep.2021.109308

DO - 10.1016/j.celrep.2021.109308

M3 - Journal article

C2 - 34233199

VL - 36

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 1

M1 - 109308

ER -

ID: 274270784