AUTHOR=Liu Chengxin , Zhou Wenjuan , Xing Xin , Chen Jiachen , Sun Chenxi , Liu Shizhou , Lou Yunxia , Jiao Jianfen , Cao Haoling , Cui Baoxia , Hong Shuhui , Ahmadi Niloufar , Tang Yuchun 

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

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 13 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2025.1674967

DOI=10.3389/fcell.2025.1674967

ISSN=2296-634X

ABSTRACT=IntroductionThe brainstem is a critical hub connecting the cerebrum and spinal cord. However, the gene regulatory dynamics during fetal brainstem development remain incompletely characterized.MethodsThis 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.ResultsOur 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.DiscussionThis work advances our understanding of brainstem development and provides a foundational resource for research into neurological disorders.