TitleA human stem cell resource to decipher the biochemical and cellular basis of neurodevelopmental defects in Lowe syndrome.
Publication TypeJournal Article
Year of Publication2022
AuthorsAkhtar BM, Bhatia P, Acharya S, Sharma S, Sharma Y, Devi ABhuvanendr, Ganapathy K, Vasudevan A, Raghu P
JournalBiol Open
Date Published2022 Jan 15
KeywordsBrain, Cell Line, Humans, Mutation, Oculocerebrorenal Syndrome, Stem Cells

Human brain development is a complex process where multiple cellular and developmental events are coordinated to generate normal structure and function. Alteration in any of these events can impact brain development, manifesting clinically as neurodevelopmental disorders. Human genetic disorders of lipid metabolism often present with features of altered brain function. Lowe syndrome (LS) is an X-linked recessive disease with features of altered brain function. LS results from mutations in OCRL1, which encodes a phosphoinositide 5-phosphatase enzyme. However, the cellular mechanisms by which loss of OCRL1 leads to brain defects remain unknown. Human brain development involves several cellular and developmental features not conserved in other species and understanding such mechanisms remains a challenge. Rodent models of LS have been generated but failed to recapitulate features of the human disease. Here we describe the generation of human stem cell lines from LS patients. Further, we present biochemical characterization of lipid metabolism in patient cell lines and demonstrate their use as a 'disease-in-a-dish' model for understanding the mechanism by which loss of OCRL1 leads to altered cellular and physiological brain development. This article has an associated First Person interview with the first author of the paper.

Alternate JournalBiol Open
PubMed ID35023542
PubMed Central IDPMC8822356
Grant ListIA/S/14/2/501540 / / Wellcome-DBT India Alliance /
/ WT_ / Wellcome Trust / United Kingdom