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| Status |
Public on Nov 02, 2024 |
| Title |
SOX6 Gatekeeps Oligodendrocyte Maturation [CUT&RUN] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Cellular maturation is an adaptive process essential for tissue formation and function, yet distinct from the initial steps of differentiation and cell fate specification. Understanding the regulation of cell maturation may inform underlying mechanisms of disease or new approaches to regenerative medicine. In the central nervous system, failed generation of mature oligodendrocytes contributes to numerous diseases including multiple sclerosis. Here, we report a transcriptional mechanism that governs the timing of oligodendrocyte maturation. After differentiation, the transcription factor SOX6 redistributes from super enhancers in proliferating oligodendrocyte progenitor cells to cluster across specific gene bodies in immature oligodendrocytes. These sites exhibit extensive chromatin decondensation and transcription, which abruptly turns off upon maturation. Suppression of SOX6 deactivates these immaturity loci, resulting in rapid transition to mature myelinating oligodendrocytes. Cells harboring this immature oligodendrocyte SOX6 gene signature are specifically enriched in multiple sclerosis patient brains, suggesting that failed maturation contributes to disease pathology. Administration of a Sox6-targeting antisense oligonucleotide in postnatal mice drove precocious oligodendrocyte maturation. Our findings reveal that SOX6 governs oligodendrocyte maturation and that its targeting could inform therapeutic strategies for enhancing myelin regeneration in neurodevelopmental and neurodegenerative diseases.
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| Overall design |
CUT & RUN of pluripotent stem cell derived oligodendrocyte progenitor cells (OPCs) and oligodendrocytes (OLs)
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| Contributor(s) |
Zhan JJ, Cohn EF, Allan KC, Tesar PJ |
| Citation missing |
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| |
| Submission date |
Nov 01, 2024 |
| Last update date |
Nov 03, 2024 |
| Contact name |
Paul Tesar |
| E-mail(s) |
[email protected]
|
| Organization name |
Case Western Reserve University
|
| Department |
Genetics & Genome Sciences
|
| Street address |
10900 Euclid Ave.
|
| City |
Cleveland |
| State/province |
Ohio |
| ZIP/Postal code |
44106 |
| Country |
USA |
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| Platforms (1) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE197319 |
SOX6 Gatekeeps Oligodendrocyte Maturation |
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| Relations |
| BioProject |
PRJNA1180921 |
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