Fig. 5: snRNA-seq reveals developmental arrest of astrocyte lineage in brain tissue of Snai2^−/− mice.

A UMAP plots and cell type composition in brain tissue of Snai2^+/+ and Snai2^−/− mice. The UMAP plots on the left panel show six cell clusters in brain tissue of Snai2^+/+(13174 cells) and Snai2^−/− (13614 cells) mice. Each colored region represents a distinct cell type, including oligodendrocyte, neuron, others, astrocyte, progenitor cell, and endothelial cell. Black dashed-line boxes delineate significant differences in both the spatial distribution and morphological characteristics of astrocytes between Snai2^+/+ and Snai2^−/− mice. The stacked bar plots on the right panel show the proportion of each of the six cell clusters in brain tissue of Snai2^+/+ and Snai2^−/− mice. B Pseudotime analysis of astrocyte lineage in brain tissue of Snai2^+/+ and Snai2^−/− mice. The UMAP plots on the left panel show the developmental trajectory of astrocyte lineage in brain tissue of Snai2^+/+ and Snai2^−/− mice. Distinct spatial patterns were observed between genotypes: in Snai2^+/+ mice, C1 astrocytes demonstrate a more concentrated distribution pattern with broader tissue coverage compared to the relatively dispersed and restricted distribution observed in Snai2^−/− mice, as demarcated by black dashed lines. The stacked bar plots on the right panel show the proportion of each of the five astrocyte clusters in brain tissue of Snai2^+/+ and Snai2^−/− mice. The red rectangular frame highlights a significantly higher proportion of C1 astrocytes in Snai2^+/+ mice compared to Snai2^−/− mice, indicating genotype-dependent differences in astrocyte subpopulation distribution. C GSVA of metabolic processes in the five astrocyte clusters (C1-C5). The GSVA plot illustrates the metabolic processes in the five astrocyte clusters, with C1 exhibiting significantly higher enrichment scores for genes involved in acetylcholine metabolism compared to other metabolic pathways. D Pseudotime trajectory of astrocyte clusters in brain tissue of Snai2^+/+ and Snai2^−/− mice. Astrocytes in Snai2^+/+ mouse predominantly differentiate into C1 and C5 clusters, while the differentiation process almost stops at C2 thereby leading to significant decreases in C1 and C5 clusters in the Snai2^−/− mouse brain. E Box plots show the predicted ordering of cell clusters within astrocyte lineage (C1-C5) based on cellular (Cyto) trajectory reconstruction analysis using gene counts and expression (CytoTRACE) scores. Higher CytoTRACE scores indicate less differentiated cells, while the comparatively lower scores observed in C1 astrocytes indicate a more terminally differentiated cellular state.