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| Status |
Public on Apr 07, 2021 |
| Title |
Expression data from Human Fetal Astrocytes and Neurons transduced with WT and mutant HTT |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Glial pathology has been implicated as a causal contributor to the dysfunction and death of striatal neurons that characterizes Huntington disease. In this study, we investigated mutant HTT (mHTT)-associated changes in gene expression by both mouse and human striatal astrocytes. Mouse striatal astrocytes were FACS-sorted from two distinct models, R6/2 and zQ175 mice, which respectively express exon1-only truncated or full-length HTT, while human astrocytes were generated from either hESCs expressing full-length mHTT, or fetal striatal glia transduced with exon1-only mHTT. Comparison of differential gene expression between each of these conditions and their normal HTT controls, and to one another, revealed astrocyte-specific alterations in both truncated and full-length mHTT models that were shared by both species, yet with differences that clearly distinguished glia derived from each model. Overlap of these data sets revealed that the patterns of mHTT-associated transcriptional dysregulation depended not only upon species, but also upon whether the astroglia expressed truncated or full-length mHTT. These data revealed a common set of conserved, mHTT-associated dysregulated pathways that may present targets for the rescue of glial pathology in HD, while revealing that the gene expression of glia expressing truncated mHTT may differ substantially from that of glia expressing full-length mHTT.
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| Overall design |
Cells from the lateral ganglionic eminence of 14-18 week gestational aged human brains were isolated, transduced with a reporter only, WT HTT, or a mutant HTT, and sorted via MACS on the absence or presence of PSA-NCAM for whole genome microarray expression analysis.
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| Contributor(s) |
Mariani JN, Benraiss A, Goldman SA |
| Citation(s) |
34233199 |
| Submission date |
Jul 09, 2020 |
| Last update date |
Jul 12, 2022 |
| Contact name |
John Mariani |
| E-mail(s) |
john_mariani@urmc.rochester.edu
|
| Organization name |
University of Rochester
|
| Department |
Neurology
|
| Lab |
Steven Goldman
|
| Street address |
601 Elmwood Avenue
|
| City |
Rochester |
| State/province |
NY |
| ZIP/Postal code |
14642 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL16686 |
[HuGene-2_0-st] Affymetrix Human Gene 2.0 ST Array [transcript (gene) version] |
|
| Samples (18)
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| This SubSeries is part of SuperSeries: |
| GSE154141 |
Cell-intrinsic glial pathology is conserved across human and murine models of Huntington Disease |
|
| Relations |
| BioProject |
PRJNA645170 |
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