Furlanetto F, Flegel N, Kremp M, Spear C, Fröb F, Alfonsetti M, Bohl B, Krumbiegel M, Turan S, Reis A, Lie DC, Winkler J, Falk S, Wegner M, Karow M (2025)
Publication Type: Journal article
Publication year: 2025
Book Volume: 8
Article Number: e202403102
Journal Issue: 6
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 oligoden-droglial 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 experi-mental strategy, we established a novel organoid model, which generates oligodendroglial cells within a human neurogenic tissue–like context. Also, here we found a reduced ability of TCF4 heterozygous cells to differentiate toward oligodendroglial cells. In sum, we establish a role of human TCF4 in oligoden-drocyte differentiation and provide a model system, which al-lows to dissect the disease etiology in a human tissue–like context.
APA:
Furlanetto, F., Flegel, N., Kremp, M., Spear, C., Fröb, F., Alfonsetti, M.,... Karow, M. (2025). A novel human organoid model system reveals requirement of TCF4 for oligodendroglial differentiation. Life Science Alliance, 8(6). https://doi.org/10.26508/lsa.202403102
MLA:
Furlanetto, Federica, et al. "A novel human organoid model system reveals requirement of TCF4 for oligodendroglial differentiation." Life Science Alliance 8.6 (2025).
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