SOX17 transcription factor negatively regulates oligodendrocyte precursor cell differentiation.
Melissa FauveauBaptiste WilmetCyrille DebouxKarelle BenardaisCorinne BachelinAna C TemporãoChristophe KerninonBrahim Nait-OumesmarPublished in: Glia (2018)
Oligodendrocyte development is a critical process timely and spatially regulated to ensure proper myelination of the central nervous system. HMG-box transcription factors are key regulators of oligodendrocyte lineage progression. Among these factors, Sox17 was previously identified as a positive regulator of oligodendrocyte development. However, the role of Sox17 in oligodendroglial cell lineage progression and differentiation is still poorly understood. To define the functional role of Sox17, we generated new transgenic mouse models with inducible overexpression of Sox17, specifically in oligodendroglial cells. Here, we report that gain of Sox17 function has no effect on oligodendrocyte progenitor cells (OPCs) specification. During early postnatal development, Sox17 overexpression increases the pool of OPCs at the expense of differentiated oligodendrocytes. However, the oligodendroglial cell population, OPC proliferation and apoptosis remained unchanged in Sox17 transgenic mice. RNA sequencing, quantitative RT-PCR and immunohistochemical analysis showed that Sox17 represses the expression of the major myelin genes, resulting in a severe CNS hypomyelination. Overall, our data highlight an unexpected role for Sox17 as a negative regulator of OPC differentiation and myelination, suggesting stage specific functions for this factor during oligodendroglial cell lineage progression.
Keyphrases
- transcription factor
- single cell
- dna binding
- genome wide identification
- stem cells
- cell therapy
- poor prognosis
- oxidative stress
- gene expression
- cell cycle arrest
- signaling pathway
- high resolution
- preterm infants
- blood brain barrier
- electronic health record
- multiple sclerosis
- mass spectrometry
- bone marrow
- dna methylation
- drug induced