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| Status |
Public on Jun 08, 2020 |
| Title |
Chromatin Accessibility and Transcription Dynamics During In Vitro Astrocyte Differentiation of Huntington’s Disease Monkey Pluripotent Stem Cells. |
| Organism |
Macaca mulatta |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Huntington’s Disease (HD) is a fatal, neurodegenerative disorder caused by a CAG repeat expansion, resulting in a mutant huntingtin protein. While it is now clear that astrocytes are affected by HD and significantly contribute to neuronal dysfunction and pathogenesis, the alterations in the transcriptional and epigenetic profiles in HD astrocytes have yet to be characterized. Here, we examined global transcription and chromatin accessibility dynamics during in vitro astrocyte differentiation in a transgenic non-human primate model of HD. We found global changed in accessibility and transcription across different stages of HD pluripotent stem cell differentiation, with distinct trends first observed in neural progenitor cells (NPCs), once cells have committed to a neural lineage. Transcription of p53 signaling and cell cycle pathway genes was highly impacted during differentiation, with depletion in HD NPCs and upregulation in HD astrocytes. E2F target genes also displayed this inverse expression pattern, and strong associations between E2F target gene expression and accessibility at nearby putative enhancers were observed. The results suggest that chromatin accessibility and transcription are altered throughout in vitro HD astrocyte differentiation and provide evidence that E2F dysregulation contributes to aberrant cell cycle reentry and apoptosis throughout the progression from NPCs to astrocytes.
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| Overall design |
RNA-seq and ATAC-seq was taken from in vitro samples of pluripotent stem cells (PSCs), neural progenitor cells, developing astrocytes, and astrocytes, all of which were derived in vitro from PSCs. PSCs were taken from macaques containing a transgene with exon 1 of the human mutant huntingtin gene (HD samples) as well as from control macaques.
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| Contributor(s) |
Goodnight AV, Kremsky I, Khampang S, Jung Y, Billingsley JM, Bosinger SE, Corces VG, Chan AW |
| Citation(s) |
31722751 |
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| Submission date |
May 01, 2019 |
| Last update date |
Sep 08, 2020 |
| Contact name |
Isaac Kremsky |
| E-mail(s) |
ikremsk@emory.edu
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| Organization name |
Emory University
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| Department |
Biology
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| Lab |
Corces
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| Street address |
1510 Clifton Rd
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| City |
Atlanta |
| State/province |
GA |
| ZIP/Postal code |
30322 |
| Country |
USA |
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| Platforms (2) |
| GPL19129 |
Illumina HiSeq 2500 (Macaca mulatta) |
| GPL23804 |
Illumina HiSeq 3000 (Macaca mulatta) |
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| Samples (40)
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| Relations |
| BioProject |
PRJNA540664 |
| SRA |
SRP194398 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE130570_RAW.tar |
3.8 Gb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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