A novel human organoid model system reveals requirement of TCF4 for oligodendroglial differentiation.

ABSTRACT: Heterozygous mutations of TCF4 in humans cause Pitt-Hopkins syndrome, a neurodevelopmental disease associated with intellectual disability and brain malformations. Although most studies focus on the role of TCF4 in neural stem cells and neurons, we here set out to assess the implication of TCF4 for oligodendroglial differentiation. We discovered that both monoallelic and biallelic mutations in TCF4 result in a diminished capacity to differentiate human neural progenitor cells toward myelinating oligodendrocytes through the forced expression of the transcription factors SOX10, OLIG2, and NKX6.2. Using this experimental strategy, we established a novel organoid model, which generates oligodendroglial cells within a human neurogenic tissue-like context. Also, here we found a red

SUBMITTER: Furlanetto F 

PROVIDER: S-EPMC11953572 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature