Human brain development is a complex process where multiple cellular and developmental events are co-ordinated 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 a X-linked recessive disease with features of altered brain function. LS results from mutations in OCRL1 that 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.
A human stem cell resource to decipher the biochemical and cellular basis of neurodevelopmental defects in Lowe Syndrome
Present address: Center for Molecular and Cellular Bioengineering (CMCB), Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany
Present address: Cardiovascular Research Unit, Department of Population Health, Luxembourg Institute of Health, Strassen, Luxembourg and Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-alzette, Luxembourg
Present address: Department of Biochemistry, Weill Cornell Medicine, New York, NY, 10065, USA
Present address: Department of Neurobiology and Behavior, Center for Nervous System Disorders, Stony Brook University, Stony Brook, NY 11794-5230, USA
- Award Group:
- Funder(s): Department of Biotechnology
- Award Id(s): BT/PR17316/MED/31/326/2015
- Funder(s):
- Award Group:
- Funder(s): Department of Atomic Energy
- Award Id(s): Project Identification No. RTI 4006
- Funder(s):
- Award Group:
- Funder(s): Pratiksha Trust
- Award Id(s): -
- Funder(s):
- Award Group:
- Funder(s): India Alliance
- Award Id(s): IA/S/14/2/501540
- Funder(s):
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Bilal M. Akhtar, Priyanka Bhatia, Shubhra Acharya, Sanjeev Sharma, Yojet Sharma, B. S. Aswathy, Kavina Ganapathy, Anil Vasudevan, Padinjat Raghu; A human stem cell resource to decipher the biochemical and cellular basis of neurodevelopmental defects in Lowe Syndrome. Biol Open 2022; bio.059066. doi: https://doi.org/10.1242/bio.059066
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