Two SVZ clusters, clusters #13 and #20, which shared a profile of cell identity markers, differed in their cell-cycle phase composition, with cluster #13 cells predominantly in G2/M phase, whereas cluster #20 was predominantly in S phase. All VZ-annotated clusters were predominantly in S and G2/M phases, and 3 out of 6 SVZ clusters were also predominantly in S and G2/M phases.
In the case of cluster #1, we also quantified the percent of cells in each cell-cycle phase in each of the sub-clusters. Graphical abstractĬell-cycle composition (proportion of cells in G1, S or G2/M phases) and pseudotime score distribution were used to further order each cell cluster within its major annotated cell-type. Thus, episodic PAE persistently alters the developing neural transcriptome, contributing to sex- and cell-type-specific teratology. PAE females exhibited neural loss of X-inactivation, with correlated activation of autosomal genes and evidence for spliceosome dysfunction. PAE inhibited Bcl11a, Htt, Ctnnb1, and other upstream regulators of differentially expressed genes and inhibited several autism-linked genes, suggesting that neurodevelopmental disorders share underlying mechanisms. Whereas most differentially regulated genes were inhibited, particularly in females, PAE also induced sex-independent neural expression of fetal hemoglobin, a presumptive epigenetic stress adaptation. We found, in an analysis of 38 distinct neural subpopulations across 8 lineage subtypes, that PAE altered neural maturation and cell cycle and disrupted gene co-expression networks. Single-cell RNA sequencing was performed on murine fetal cerebral cortical cells from six timed pregnancies, to decipher persistent cell- and sex-specific effects of an episode of PAE during early neurogenesis. Prenatal alcohol exposure (PAE) results in cerebral cortical dysgenesis.
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