Characterization of Bipolar Disorder Patient-Specific Induced Pluripotent Stem Cells from a Family Reveals Neurodevelopmental and mRNA Expression Abnormalities

DSpace/Manakin Repository

Characterization of Bipolar Disorder Patient-Specific Induced Pluripotent Stem Cells from a Family Reveals Neurodevelopmental and mRNA Expression Abnormalities

Citable link to this page

 

 
Title: Characterization of Bipolar Disorder Patient-Specific Induced Pluripotent Stem Cells from a Family Reveals Neurodevelopmental and mRNA Expression Abnormalities
Author: Madison, Jon M.; Zhou, Fen; Nigam, Aparna; Hussain, Ali; Barker, Douglas D.; Nehme, Ralda; van der Ven, Karlijn; Hsu, Jenny; Wolf, Pavlina; Fleishman, Morgan; O’Dushlaine, Colm; Rose, Sam; Chambert, Kimberly; Lau, Frank H.; Ahfeldt, Tim; Rueckert, Erroll H.; Sheridan, Steven D.; Fass, Daniel M.; Nemesh, James; Mullen, Thomas E.; Daheron, Laurence; McCarroll, Steve; Sklar, Pamela; Perlis, Roy H.; Haggarty, Stephen J.

Note: Order does not necessarily reflect citation order of authors.

Citation: Madison, J. M., F. Zhou, A. Nigam, A. Hussain, D. D. Barker, R. Nehme, K. van der Ven, et al. 2014. “Characterization of Bipolar Disorder Patient-Specific Induced Pluripotent Stem Cells from a Family Reveals Neurodevelopmental and mRNA Expression Abnormalities.” Molecular psychiatry 20 (6): 703-717. doi:10.1038/mp.2015.7. http://dx.doi.org/10.1038/mp.2015.7.
Full Text & Related Files:
Abstract: Bipolar disorder (BD) is a common neuropsychiatric disorder characterized by chronic recurrent episodes of depression and mania. Despite evidence for high heritability of BD, little is known about its underlying pathophysiology. To develop new tools for investigating the molecular and cellular basis of BD we applied a family-based paradigm to derive and characterize a set of 12 induced pluripotent stem cell (iPSC) lines from a quartet consisting of two BD-affected brothers and their two unaffected parents. Initially, no significant phenotypic differences were observed between iPSCs derived from the different family members. However, upon directed neural differentiation we observed that CXCR4 (CXC chemokine receptor-4) expressing central nervous system (CNS) neural progenitor cells (NPCs) from both BD patients compared to their unaffected parents exhibited multiple phenotypic differences at the level of neurogenesis and expression of genes critical for neuroplasticity, including WNT pathway components and ion channel subunits. Treatment of the CXCR4+ NPCs with a pharmacological inhibitor of glycogen synthase kinase 3 (GSK3), a known regulator of WNT signaling, was found to rescue a progenitor proliferation deficit in the BD-patient NPCs. Taken together, these studies provide new cellular tools for dissecting the pathophysiology of BD and evidence for dysregulation of key pathways involved in neurodevelopment and neuroplasticity. Future generation of additional iPSCs following a family-based paradigm for modeling complex neuropsychiatric disorders in conjunction with in-depth phenotyping holds promise for providing insights into the pathophysiological substrates of BD and is likely to inform the development of targeted therapeutics for its treatment and ideally prevention.
Published Version: doi:10.1038/mp.2015.7
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4440839/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:23993612
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters