Abstract
SUMMARYTransdifferentiation, or direct cell reprogramming, is the direct conversion of one fully differentiated cell type into another. Whether core mechanisms are shared between different transdifferentiation events, which can occur naturally in presence or in absence of cell division, is unclear. Our lab has previously characterized the Y-to-PDA natural transdifferentiation in Caenorhabditis elegans, which occurs without cell division and requires orthologs of vertebrates’ reprogramming factors. In this study, focusing on another transdifferentiation process, the K rectal cell-to-DVB GABAergic neuron, we report that the Y-to-PDA reprogramming factor SEM-4/SALL, SOX-2, CEH-6/POU are required for K-to-DVB transdifferentiation to allow the erasure of the rectal identity. In addition, cell division is necessary but not sufficient for this transdifferentiation event while the Wnt signaling plays distinct functions during the process including the selection of the daughter cell with a different fate, loss of the rectal identity and imposition of the specific neuronal subtype identity. We provide evidence that both the Wnt signaling and Y-to-PDA reprogramming factor SEM-4/SALL, SOX-2, CEH-6/POU act in parallel for the rectal identity erasure. Our results further support a model where antagonistic activities of SOX-2 and POP-1 and decreasing SOX-2 levels over time provide a timer for the acquisition of the final identity. In addition, the different levels of SOX-2 provide a mechanism for the integration of Wnt opposite dedifferentiation and re-differentiation functions during K-to-DVB transdifferentiation.
Publisher
Cold Spring Harbor Laboratory
Reference98 articles.
1. Oct-3/4 regulates stem cell identity and cell fate decisions by modulating Wnt/β-catenin signalling
2. Ahier, A. , Suman, S.K. , and Jarriault, S. (2020). Gene bashing of ceh-6 locus identifies genomic regions important for ceh-6 rectal cell expression and rescue of its mutant lethality. MicroPubl Biol 2020.
3. Interactions between Sox9 and β-catenin control chondrocyte differentiation
4. Wnt Signaling and a Hox Protein Cooperatively Regulate PSA-3/Meis to Determine Daughter Cell Fate after Asymmetric Cell Division in C. elegans
5. Armenti, S.T. , and Nance, J. (2012). Adherens Junctions in C. elegans Embryonic Morphogenesis. In Adherens Junctions: From Molecular Mechanisms to Tissue Development and Disease, T. Harris , ed. (Dordrecht: Springer Netherlands), pp. 279–299.