Neurodevelopmental defects in human cortical organoids with N-acetylneuraminic acid synthase mutation.

ABSTRACT: Biallelic genetic variants in N-acetylneuraminic acid synthase (NANS), a critical enzyme in endogenous sialic acid biosynthesis, are clinically associated with neurodevelopmental disorders. However, the mechanism underlying the neuropathological consequences has remained elusive. Here, we found that NANS mutation resulted in the absence of both sialic acid and protein polysialylation in the cortical organoids and notably reduced the proliferation and expansion of neural progenitors. NANS mutation dysregulated neural migration and differentiation, disturbed synapse formation, and weakened neuronal activity. Single-cell RNA sequencing revealed that NANS loss of function markedly altered transcriptional programs involved in neuronal differentiation and ribos

SUBMITTER: Bu Q 

PROVIDER: S-EPMC10672180 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature