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A circular RNA expressed from the FAT3 locus regulates neural development

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Item Type:Article
Title:A circular RNA expressed from the FAT3 locus regulates neural development
Creators Name:Seeler, S. and Andersen, M.S. and Sztanka-Toth, T. and Rybiczka-Tešulov, M. and van den Munkhof, M.H. and Chang, C.C. and Maimaitili, M. and Venø, M.T. and Hansen, T.B. and Pasterkamp, R.J. and Rybak-Wolf, A. and Denham, M. and Rajewsky, N. and Kristensen, L.S. and Kjems, J.
Abstract:Circular RNAs (circRNAs) are key regulators of cellular processes, are abundant in the nervous system, and have putative regulatory roles during neural differentiation. However, the knowledge about circRNA functions in brain development is limited. Here, using RNA-sequencing, we show that circRNA levels increased substantially over the course of differentiation of human embryonic stem cells into rostral and caudal neural progenitor cells (NPCs), including three of the most abundant circRNAs, ciRS-7, circRMST, and circFAT3. Knockdown of circFAT3 during early neural differentiation resulted in minor transcriptional alterations in bulk RNA analysis. However, single-cell transcriptomics of 30 and 90 days differentiated cerebral organoids deficient in circFAT3 showed a loss of telencephalic radial glial cells and mature cortical neurons, respectively. Furthermore, non-telencephalic NPCs in cerebral organoids showed changes in the expression of genes involved in neural differentiation and migration, including FAT4, ERBB4, UNC5C, and DCC. In vivo depletion of circFat3 in mouse prefrontal cortex using in utero electroporation led to alterations in the positioning of the electroporated cells within the neocortex. Overall, these findings suggest a conserved role for circFAT3 in neural development involving the formation of anterior cell types, neuronal differentiation, or migration.
Keywords:ncRNAs, circRNAs, Cerebral Organoids, scRNA-seq, Neural Development, circFAT3, Animals, Mice
Source:Molecular Neurobiology
Publisher:Springer / Humana Press
Page Range:3239–3260
Date:June 2023
Official Publication:https://doi.org/10.1007/s12035-023-03253-7
PubMed:View item in PubMed

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