A Circular RNA Expressed from the FAT3 Locus Regulates Neural Development.
Cerebral organoids
Neural development
circFAT3
circRNAs
ncRNAs
scRNA-seq
Journal
Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963
Informations de publication
Date de publication:
Jun 2023
Jun 2023
Historique:
received:
27
07
2022
accepted:
28
01
2023
medline:
25
4
2023
pubmed:
26
2
2023
entrez:
25
2
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36840844
doi: 10.1007/s12035-023-03253-7
pii: 10.1007/s12035-023-03253-7
pmc: PMC10122638
doi:
Substances chimiques
RNA, Circular
0
FAT3 protein, human
0
Epidermal Growth Factor
62229-50-9
Cadherins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3239-3260Subventions
Organisme : H2020 Marie Skłodowska-Curie Actions
ID : 721890-circRTrain
Organisme : Villum Fonden
ID : 13393
Organisme : Carlsbergfondet
ID : CF16-0087
Organisme : Lundbeckfonden
ID : DANDRITE- R248-2016-2518
Informations de copyright
© 2023. The Author(s).
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