Tissue block-resolved developmental transcriptomic atlas of human fetal brainstem reveals gene modules with implications for neurological disorders.

INTRODUCTION

The brainstem is a critical hub connecting the cerebrum and spinal cord. However, the gene regulatory dynamics during fetal brainstem development remain incompletely characterized.

METHODS

This study employed RNA-seq to map transcriptomes across 107 tissue blocks from 18 human fetal brainstems (gestational weeks 9-33). Weighted gene co-expression network analysis (WGCNA) identified 22 functionally annotated modules. We quantitatively assessed their spatiotemporal activity gradients and systematically classified genes exhibiting significant temporal trajectories based on phase-specific signatures.

RESULTS

Our integrated approach constructed a developmental transcriptomic profile, revealing stage-specific regulatory networks and dynamic transcriptional trajectories governing ontogeny. Crucially, we validated the expression of neurodevelopmental disorder-associated genes within fetal brainstem tissues.

DISCUSSION: This work advances our understanding of brainstem development and provides a foundational resource for research into neurological disorders.