Induced pluripotent stem cell models of Zellweger spectrum disorder show impaired peroxisome assembly and cell type-specific lipid abnormalities

Stem Cell Research & Therapy
Xiao-Ming WangJoseph G Hacia

Abstract

Zellweger spectrum disorder (PBD-ZSD) is a disease continuum caused by mutations in a subset of PEX genes required for normal peroxisome assembly and function. They highlight the importance of peroxisomes in the development and functions of the central nervous system, liver, and other organs. To date, the underlying bases for the cell-type specificity of disease are not fully elucidated. Primary skin fibroblasts from seven PBD-ZSD patients with biallelic PEX1, PEX10, PEX12, or PEX26 mutations and three healthy donors were transduced with retroviral vectors expressing Yamanaka reprogramming factors. Candidate induced pluripotent stem cells (iPSCs) were subject to global gene expression, DNA methylation, copy number variation, genotyping, in vitro differentiation and teratoma formation assays. Confirmed iPSCs were differentiated into neural progenitor cells (NPCs), neurons, oligodendrocyte precursor cells (OPCs), and hepatocyte-like cell cultures with peroxisome assembly evaluated by microscopy. Saturated very long chain fatty acid (sVLCFA) and plasmalogen levels were determined in primary fibroblasts and their derivatives. iPSCs were derived from seven PBD-ZSD patient-derived fibroblasts with mild to severe peroxisome assembly d...Continue Reading

References

May 22, 2002·The Journal of Clinical Investigation·Robert E SchwartzCatherine M Verfaillie
Apr 21, 2004·American Journal of Medical Genetics. Part a·Bwee Tien Poll-ThePeter G Barth
Oct 7, 2004·Journal of the American Society for Mass Spectrometry·Karin A Zemski Berry, Robert C Murphy
Feb 26, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ruud DirkxMyriam Baes
Jun 8, 2006·Annual Review of Biochemistry·Ronald J A Wanders, Hans R Waterham
Oct 24, 2006·Biochimica Et Biophysica Acta·Steven J SteinbergHugo W Moser
Mar 10, 2007·Journal of Inherited Metabolic Disease·N Shimozawa
Mar 30, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Megan H KeanePhyllis L Faust
Apr 20, 2007·Biochemical and Biophysical Research Communications·Ruud DirkxPaul P Van Veldhoven
Jul 24, 2007·Nature Genetics·Celia M KassmannKlaus-Armin Nave
Dec 15, 2007·Nature Protocols·Kazutoshi TakahashiShinya Yamanaka
Feb 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·W E LowryK Plath
Apr 17, 2008·Journal of Inherited Metabolic Disease·S WellerJ Gärtner
Jun 26, 2008·Nature Clinical Practice. Gastroenterology & Hepatology·Shikha S SundaramRonald J Sokol
Jul 5, 2008·Nature Protocols·In-Hyun ParkGeorge Q Daley
Aug 21, 2008·Medical & Biological Engineering & Computing·Zhi WangQiuyan Dai
Oct 8, 2008·Journal of Lipid Research·Young-Ah MoonJay D Horton
Jan 15, 2009·European Journal of Human Genetics : EJHG·Cindy KrauseJutta Gärtner
Apr 21, 2009·Methods in Molecular Biology·Xiaofeng Xia, Su-Chun Zhang
Apr 21, 2009·Methods in Molecular Biology·Maya N HatchHans S Keirstead
May 9, 2009·Current Opinion in Cell Biology·Miguel A Andrade-NavarroHeidi M McBride
Aug 12, 2009·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Myriam Baes, Patrick Aubourg
Aug 22, 2009·Nature Protocols·Bao-Yang Hu, Su-Chun Zhang
Oct 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·Noriyuki KanzawaTaroh Kinoshita
Jan 14, 2010·Journal of Cellular Biochemistry·Xiao-Ming WangJoseph G Hacia
Feb 12, 2010·Cold Spring Harbor Protocols·Yipeng WangXiao-Qin Xia
Feb 18, 2010·Proceedings of the National Academy of Sciences of the United States of America·Bao-Yang HuSu-Chun Zhang
Mar 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Rui ZhangNancy Braverman
Mar 30, 2010·Biochimica Et Biophysica Acta·M IslingerM Schrader

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Citations

Mar 7, 2018·Journal of Pediatric Gastroenterology and Nutrition·Sakil Kulkarni, David A Rudnick
Mar 27, 2020·Frontiers in Cellular Neuroscience·Ndidi-Ese UzorAndrey S Tsvetkov
Oct 18, 2015·BMC Research Notes·Krishna RamaswamyJoseph G Hacia
Dec 6, 2019·Frontiers in Medicine·James L Corbett, Stephen A Duncan
Jul 15, 2020·Clinical Pharmacology and Therapeutics·Sara L Van Driest, Piet H van der Graaf

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Datasets Mentioned

BETA
GSE43996
GSE68134
GSE69066

Methods Mentioned

BETA
genotyping
FACS
Assay
ELISA
PCR
dissection
genetic modifications

Software Mentioned

GenomeStudio
CNVPartition
Partek Genomics Suite
Ingenuity Pathways Analysis ( IPA )
DAVID
WebGestalt
WebArray

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