Transcriptomics

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Single-nuclus sequencing analysis reveals aberrant brain development in fetuses with neural tube defects


ABSTRACT: Background: Neural tube defects (NTDs) are congenital malformations that occur when the neural tube fails to close properly during early embryonic development. However, the identity of affected celltypes and pathogenic mechanisms remain unclear due to the lack of clinical samples. Method: We utilized single-nucleus RNA sequencing to analyze 37,064 neural tube cells from NTDs and normal abortus at 14 and 15 gestational weeks. Multiplexed immunofluorescence staining was performed to further validate some phenotypes. Results: Firstly, we revealed that the most affected celltypes are excitatory neurons, inhibitory neurons, and astrocytes. We further elucidated that the main subtypes mediating abnormal development in NTDs is IGF2high subtypes in inhibitory neurons and MEG3high subtypes in astrocytes. Importantly, our findings highlighted IGF2 as a pivotal gene for abnormal development and abnormal cell-cell communications in NTDs. Conclusions: In summary, this study presents the first single-cell atlas of NTDs and provides new insights for further research into the underlying mechanisms of NTDs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE266595 | GEO | 2024/05/15

REPOSITORIES: GEO

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