Modeling neurological diseases with induced pluripotent cells reprogrammed from immortalized lymphoblastoid cell lines

Modeling neurological diseases with induced pluripotent cells reprogrammed from immortalized lymphoblastoid cell lines

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 ski...

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Main Authors: Fujimori, Koki, Tezuka, Toshiki, Ishiura, Hiroyuki, Mitsui, Jun, Doi, Koichiro, Yoshimura, Jun, Tada, Hirobumi, Matsumoto, Takuya, Isoda, Miho, Hashimoto, Ryota, Hattori, Nubutaka, Takahashi, Takuya, Morishita, Shinichi, Tsuji, Shoji, Akamatsu, Wado, Okano, Hideyuki
Format: Online
Language:English
Published: BioMed Central 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5046991/
id pubmed-5046991
recordtype oai_dc
spelling pubmed-50469912016-10-11 Modeling neurological diseases with induced pluripotent cells reprogrammed from immortalized lymphoblastoid cell lines Fujimori, Koki Tezuka, Toshiki Ishiura, Hiroyuki Mitsui, Jun Doi, Koichiro Yoshimura, Jun Tada, Hirobumi Matsumoto, Takuya Isoda, Miho Hashimoto, Ryota Hattori, Nubutaka Takahashi, Takuya Morishita, Shinichi Tsuji, Shoji Akamatsu, Wado Okano, Hideyuki Research 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. BioMed Central 2016-10-03 /pmc/articles/PMC5046991/ /pubmed/27716287 http://dx.doi.org/10.1186/s13041-016-0267-6 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Fujimori, Koki
Tezuka, Toshiki
Ishiura, Hiroyuki
Mitsui, Jun
Doi, Koichiro
Yoshimura, Jun
Tada, Hirobumi
Matsumoto, Takuya
Isoda, Miho
Hashimoto, Ryota
Hattori, Nubutaka
Takahashi, Takuya
Morishita, Shinichi
Tsuji, Shoji
Akamatsu, Wado
Okano, Hideyuki
spellingShingle Fujimori, Koki
Tezuka, Toshiki
Ishiura, Hiroyuki
Mitsui, Jun
Doi, Koichiro
Yoshimura, Jun
Tada, Hirobumi
Matsumoto, Takuya
Isoda, Miho
Hashimoto, Ryota
Hattori, Nubutaka
Takahashi, Takuya
Morishita, Shinichi
Tsuji, Shoji
Akamatsu, Wado
Okano, Hideyuki
Modeling neurological diseases with induced pluripotent cells reprogrammed from immortalized lymphoblastoid cell lines
author_facet Fujimori, Koki
Tezuka, Toshiki
Ishiura, Hiroyuki
Mitsui, Jun
Doi, Koichiro
Yoshimura, Jun
Tada, Hirobumi
Matsumoto, Takuya
Isoda, Miho
Hashimoto, Ryota
Hattori, Nubutaka
Takahashi, Takuya
Morishita, Shinichi
Tsuji, Shoji
Akamatsu, Wado
Okano, Hideyuki
author_sort Fujimori, Koki
title Modeling neurological diseases with induced pluripotent cells reprogrammed from immortalized lymphoblastoid cell lines
title_short Modeling neurological diseases with induced pluripotent cells reprogrammed from immortalized lymphoblastoid cell lines
title_full Modeling neurological diseases with induced pluripotent cells reprogrammed from immortalized lymphoblastoid cell lines
title_fullStr Modeling neurological diseases with induced pluripotent cells reprogrammed from immortalized lymphoblastoid cell lines
title_full_unstemmed Modeling neurological diseases with induced pluripotent cells reprogrammed from immortalized lymphoblastoid cell lines
title_sort modeling neurological diseases with induced pluripotent cells reprogrammed from immortalized lymphoblastoid cell lines
description 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.
publisher BioMed Central
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5046991/
_version_ 1613670017711210496

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