Deciphering Cell-Type and Temporal-Specific Matrisome Expression Signatures in Human Cortical Development and Neurodevelopmental Disorders via scRNA-Seq Meta-Analysis

Abstract

Human cortical development is a complex process involving the proliferation, differentiation, and migration of progenitor cells, all coordinated within a dynamic extracellular matrix (ECM). ECM plays a crucial role in guiding these processes, yet its specific contributions and the implications of its dysregulation in neurodevelopmental disorders (NDDs) remain underexplored. In this study, we conducted a meta-analysis of single-cell RNA sequencing (scRNA-seq) data from 37 donors, gestational weeks (GWs) 8 to 26 across six independent studies to elucidate cell type-specific matrisome gene expression signatures and their dynamics in the developing human cortex. Our analysis identified distinct matrisome gene signatures across various cell types, with significant temporal changes during cortical development. Notably, a substantial proportion of matrisome genes are associated with NDDs, exhibiting cell type, temporal and disease specificity. These findings highlight the critical role of cell type-specific matrisome regulation in cortical development and its potential involvement in NDD pathogenesis. This study provides a comprehensive map of cell type-specific matrisome signatures in the developing human cortex and highlights the importance of ECM in both normal development and the pathogenesis of NDDs.