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

Koki Fujimori, Toshiki Tezuka, Hiroyuki Ishiura, Jun Mitsui, Koichiro Doi, Jun Yoshimura, Hirobumi Tada, Takuya Matsumoto, Miho Isoda, Ryota Hashimoto, Nubutaka Hattori, Takuya Takahashi, Shinichi Morishita, Shoji Tsuji, Wado Akamatsu, Hideyuki Okano

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1-14
Number of pages14
JournalMolecular Brain
Volume9
Issue number1
DOIs
Publication statusPublished - 2016 Oct 3

Fingerprint

Induced Pluripotent Stem Cells
Cell Line
B-Lymphocytes
Fibroblasts
Skin
Parkinson Disease
Genome
Comparative Genomic Hybridization
Drug Discovery
Clone Cells
Tissue Donors
T-Lymphocytes
Phenotype
Biopsy
Neurons

Keywords

  • Disease modeling
  • Genomic mutation in reprogramming process
  • Induced pluripotent stem cells
  • Lymphoblastoid B-cell line
  • Neurological disorder

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

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.

In: Molecular Brain, Vol. 9, No. 1, 03.10.2016, p. 1-14.

Research output: Contribution to journalArticle

Fujimori, K, Tezuka, T, Ishiura, H, Mitsui, J, Doi, K, Yoshimura, J, Tada, H, Matsumoto, T, Isoda, M, Hashimoto, R, Hattori, N, Takahashi, T, Morishita, S, Tsuji, S, Akamatsu, W & Okano, H 2016, 'Modeling neurological diseases with induced pluripotent cells reprogrammed from immortalized lymphoblastoid cell lines', Molecular Brain, vol. 9, no. 1, pp. 1-14. https://doi.org/10.1186/s13041-016-0267-6
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. In: Molecular Brain. 2016 ; Vol. 9, No. 1. pp. 1-14.
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