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| Status |
Public on Oct 20, 2020 |
| Title |
Non-Canonical Targets of HIF1a Impair Oligodendrocyte Progenitor Cell Function [ChIP-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Mammalian cells respond to insufficient oxygen through transcriptional regulators called hypoxia-inducible factors (HIFs). Although transiently protective, prolonged HIF activity drives distinct pathological responses in different tissues. Using a model of chronic HIF1a accumulation in pluripotent-stem-cell-derived oligodendrocyte progenitors (OPCs), we demonstrate that HIF1a activates non-canonical targets to impair generation of oligodendrocytes from OPCs. HIF1a activated a unique set of genes in OPCs through interaction with the OPC-specific transcription factor OLIG2. Non-canonical targets, including Ascl2 and Dlx3, were sufficient to block differentiation through suppression of the oligodendrocyte regulator Sox10. Chemical screening revealed that inhibition of MEK/ERK signaling overcame the HIF1a-mediated block in oligodendrocyte generation by restoring Sox10 expression without affecting canonical HIF1a activity. MEK/ERK inhibition also drove oligodendrocyte formation in hypoxic regions of human oligocortical spheroids. This work defines mechanisms by which HIF1a impairs oligodendrocyte formation and establishes that cell-type-specific HIF1a targets perturb cell function in response to low oxygen.
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| Overall design |
This subseries consists of biological replicates (A and B) of ChIP-seq experiments in VHL knockout and control OPCs for HIF1a, HIF1b, H3K27Ac, and Olig2 and biological replicates (A and B) of HA ChIP-seq in HA-Ascl2 overexpression and control OPCs. Inputs used to analyze ChIP-seq for each antigen are also provided.
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| Contributor(s) |
Allan K, Morton A, Tesar P |
| Citation(s) |
33091368 |
| |
| Submission date |
Jan 10, 2020 |
| Last update date |
Jan 19, 2021 |
| Contact name |
Paul Tesar |
| E-mail(s) |
paul.tesar@case.edu
|
| Organization name |
Case Western Reserve University
|
| Department |
Genetics & Genome Sciences
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| Street address |
10900 Euclid Ave.
|
| City |
Cleveland |
| State/province |
Ohio |
| ZIP/Postal code |
44106 |
| Country |
USA |
| |
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| Platforms (3) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (25)
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| This SubSeries is part of SuperSeries: |
| GSE143474 |
Non-Canonical Targets of HIF1a Impair Oligodendrocyte Progenitor Cell Function |
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| Relations |
| BioProject |
PRJNA600555 |
| SRA |
SRP241267 |
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