Modeling neurological diseases with induced pluripotent cells reprogrammed from immortalized lymphoblastoid cell linesReport as inadecuate

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Molecular Brain

, 9:88

First Online: 03 October 2016Received: 27 June 2016Accepted: 20 September 2016


Patient-specific induced pluripotent stem cells iPSCs facilitate understanding of the etiology of diseases, discovery of new drugs and development of novel therapeutic interventions. A frequently used starting source of cells for generating iPSCs has been dermal fibroblasts DFs isolated from skin biopsies. However, there are also numerous repositories containing lymphoblastoid B-cell lines LCLs generated from a variety of patients. To date, this rich bioresource of LCLs has been underused for generating iPSCs, and its use would greatly expand the range of targeted diseases that could be studied by using patient-specific iPSCs. However, it remains unclear whether patient’s LCL-derived iPSCs LiPSCs can function as a disease model. Therefore, we generated Parkinson’s disease patient-specific LiPSCs and evaluated their utility as tools for modeling neurological diseases. We established iPSCs from two LCL clones, which were derived from a healthy donor and a patient carrying PARK2 mutations, by using existing non-integrating episomal protocols. Whole genome sequencing WGS and comparative genomic hybridization CGH analyses showed that the appearance of somatic variations in the genomes of the iPSCs did not vary substantially according to the original cell types LCLs, T-cells and fibroblasts. Furthermore, LiPSCs could be differentiated into functional neurons by using the direct neurosphere conversion method dNS method, and they showed several Parkinson’s disease phenotypes that were similar to those of DF-iPSCs. These data indicate that the global LCL repositories can be used as a resource for generating iPSCs and disease models. Thus, LCLs are the powerful tools for generating iPSCs and modeling neurological diseases.

KeywordsLymphoblastoid B-cell line Disease modeling Neurological disorder Induced pluripotent stem cells Genomic mutation in reprogramming process AbbreviationsCGHComparative genomic hybridization

DFDermal fibroblasts

DF-iPSCDF-derived iPSC

dNS methodDirect neurosphere conversion method

EBVEpstein-Barr virus

iPSCInduced pluripotent stem cells

LCLLymphoblastoid B-cell lines

LiPSCLCL-derived iPSC

mDANMidbrain dopaminergic neuron


ROSReactive oxygen species

SNVSingle nucleotide variation

SVStructural variation

THTyrosine hydroxylase

TiPSCT-cell derived iPSC

WGSWhole genome sequencing

Electronic supplementary materialThe online version of this article doi:10.1186-s13041-016-0267-6 contains supplementary material, which is available to authorized users.

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Author: Koki Fujimori - Toshiki Tezuka - Hiroyuki Ishiura - Jun Mitsui - Koichiro Doi - Jun Yoshimura - Hirobumi Tada - Takuya Mat


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