Article: Notch Inhibition Enhances Morphological Reprogramming of microRNA-Induced Human Neurons.
bioRxiv : the preprint server for biology
2024
Abstract: Although the importance of Notch signaling in brain development is well-known, its specific contribution to cellular reprogramming remains less defined. Here, we use microRNA-induced neurons that are directly reprogrammed from human fibroblasts to ... ...
| Abstract | Although the importance of Notch signaling in brain development is well-known, its specific contribution to cellular reprogramming remains less defined. Here, we use microRNA-induced neurons that are directly reprogrammed from human fibroblasts to determine how Notch signaling contributes to neuronal identity. We found that inhibiting Notch signaling led to an increase in neurite extension, while activating Notch signaling had the opposite effect. Surprisingly, Notch inhibition during the first week of reprogramming was both necessary and sufficient to enhance neurite outgrowth at a later timepoint. This timeframe is when the reprogramming miRNAs, miR-9/9* and miR-124, primarily induce a post-mitotic state and erase fibroblast identity. Accordingly, transcriptomic analysis showed that the effect of Notch inhibition was likely due to improvements in fibroblast fate erasure and silencing of anti-neuronal genes. To this effect, we identify |
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| Language | English |
| Publishing date | 2024-01-12 |
| Publishing country | United States |
| Document type | Preprint |
| DOI | 10.1101/2024.01.12.575384 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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