FADS2 disruption alters expression of neurodevelopmental genes in a human iPSC-derived model

Nicholls, Callum 2025. FADS2 disruption alters expression of neurodevelopmental genes in a human iPSC-derived model. MPhil Thesis, Cardiff University. Item availability restricted.

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Abstract

Long-chain polyunsaturated fatty acids (long-chain PUFAs) are increasingly known to be important for nervous system development and function, and disruptions in the endogenous synthesis of long-chain PUFAs have been implicated as contributing to the risk of developing neuropsychiatric disorders. However, the mechanisms by which long-chain PUFA metabolism influences neurodevelopment remain poorly understood. Here, I generated mutant human induced pluripotent stem cells (iPSCs) with reduced expression of the PUFA-metabolising enzyme FADS2 and differentiated them into cortical glutamatergic neurons using dual SMAD inhibition. These mutants showed altered expression of key developmental markers, including reduced FOXG1 expression during differentiation and altered expression of MAP2 and synaptic genes at 70 days. Furthermore, I observed changes in expression of markers associated with excitatory and inhibitory activity, highlighting potential avenues for further investigation into neuronal dysfunction in this model. These findings provide potential new directions for research into the role of long-chain PUFA metabolism in neurodevelopment and offer a foundation for exploring its contribution to neuropsychiatric diseases.

Item Type:	Thesis (MPhil)
Date Type:	Completion
Status:	Unpublished
Schools:	Schools > Biosciences
Subjects:	Q Science > Q Science (General)
Date of First Compliant Deposit:	27 November 2025
Last Modified:	28 Nov 2025 17:27
URI:	https://orca.cardiff.ac.uk/id/eprint/182724

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