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
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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.
Original language | English |
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Article number | 109308 |
Journal | Cell Reports |
Volume | 36 |
Issue number | 1 |
Number of pages | 25 |
ISSN | 2211-1247 |
DOIs | |
Publication status | Published - 2021 |
- MUTANT HUNTINGTIN, GENE-EXPRESSION, TRANSCRIPTIONAL PROFILES, CHOLESTEROL-BIOSYNTHESIS, DECREASED EXPRESSION, PROGENITOR CELLS, MOUSE MODEL, CAG REPEAT, MICROGLIA, ASTROCYTES
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