Integrative Single-Cell Analysis Decodes Gene Expression and Chromatin Accessibility in the Developing Human Fetal Brain.

Abstract

The brain is the core of the central nervous system, responsible for regulating and integrating various physiological and psychological functions. Abnormal disruptions in genes during brain development can lead to a range of neurodevelopmental disorders. In this study, we performed a systematic investigation of human fetal brain tissue from miscarriages between 8 and 17 weeks of gestation using integrated single-cell RNA sequencing (scRNA-seq) and single-cell transposase-accessible chromatin sequencing (scATAC-seq). We constructed single-cell transcriptomic and epigenomic maps of neurodevelopment, revealing key signaling pathways involved in neural cell proliferation, differentiation, and functional maturation. Through pseudotime analysis, we reconstructed the developmental trajectory of neuronal differentiation and its dynamic regulatory mechanisms. Additionally, we identified cell type-specific chromatin accessibility regions during neurogenesis and, through integrated analysis, predicted potential regulatory elements involved in the process. Overall, the single-cell multi-omics integration map constructed in this study provides valuable resources for a deeper understanding of fetal brain development, cellular heterogeneity, lineage relationships, and transcriptional regulatory networks during neurogenesis.