Single-nucleus and spatial transcriptomics of paediatric ovary: Molecular insights into the dysregulated signalling pathways underlying premature ovarian insufficiency in classic galactosemia

Abstract

	•Created a comprehensive single-nucleus transcriptomic atlas and spatial landscape of paediatric ovary tissue from prepubertal girls diagnosed with classic galactosemia (CG).
	•Our transcriptomic analysis revealed activation of genes associated with ER-stress signalling, oxidative stress response and ATM signalling/DNA damage response as shown by significant increase in expression of p-EIF2A, p-H2A.X and LC3A/B in the primordial follicles of CG ovary.
	•PTEN/PI3K/AKT signalling pathways was dysregulated evidenced by a significant reduction in phospho-AKT expression in the primordial follicles of CG ovary, suggesting impaired follicle activation and survival.

Keywords

classic galactosemia / human ovary / premature ovarian insufficiency / primordial follicles / single-nucleus RNA sequencing / spatial transcriptomics

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RIGHTS & PERMISSIONS

2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.