Temporal transcriptome analysis of neuronal commitment reveals the preeminent role of the divergent lncRNA biotype and a critical candidate gene during differentiation

摘要

A synopsis of lncRNA biotypes during cortical neuronal differentiation. Percentage of lncRNA biotype-associated coding genes with ≥1 RPKM value during in vitro cortecogenesis. Percentage of lncRNA biotype-associated coding genes significantly involved in neuronal differentiation as per the Gene Ontology database. Change in the percentage of lncRNA biotype-associated coding genes during neuronal differentiation as compared with overall cortical differentiation. – Topological overlapping matrix generated using WGCNA on expression data of different lncRNA biotypes. Clustering is based on the comparison of overall corticogenesis with neurogenesis. Maximum numbers of lncRNA gene-forming clusters during neuronal differentiation belong to the XH biotypes, followed by IG, XI, and SD. While SU and XO do not show any cluster with significantly higher membership score. – M-fuzz clustering analysis of different lncRNA biotypes at different stages of cortical neuronal differentiation. The upper panel shows the expression association of different biotypes of lncRNA-associated genes with D0- (Pluripotency) stage markers (POU5F (OCT4), NANOG, NODAL, and TDGF). The clustering sharply drops from day 0 to day 7. The middle panel shows the expression association of different biotypes of lncRNA genes associated with D7- (neuronal commitment) stage markers (PAX6 and SOX1). Clustering has sharply increased from day 0 to day 7. The lower panel shows the expression association of different biotypes of lncRNA-associated genes with later development-stage markers (EMX2, TBR1, CTIP2, CACNA1E, PRSS12, and CARTPT). The number of lncRNA biotype-associated genes enriched at different stages of cortical neuronal development. IG with a maximum number of genes involved, which are around 30 and at D0 and later development stage, respectively, while at D7, XH biotypes showing the maximum involvement that is around 30.