Title

A comprehensive library of familial human amyotrophic lateral sclerosis induced pluripotent stem cells

Authors

Ying Li, Department of Neurology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, 21205, United States of America; Brain Science Institute, Johns Hopkins University, Baltimore, Maryland, 21205, United States of America.
Umamahesw Balasubramanian, Department of Neurology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, 21205, United States of America; Brain Science Institute, Johns Hopkins University, Baltimore, Maryland, 21205, United States of America.
Devon Cohen, Department of Neurology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, 21205, United States of America; Brain Science Institute, Johns Hopkins University, Baltimore, Maryland, 21205, United States of America.
Ping-Wu Zhang, Department of Neurology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, 21205, United States of America; Brain Science Institute, Johns Hopkins University, Baltimore, Maryland, 21205, United States of America.
Elizabeth Mosmiller, Department of Neurology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, 21205, United States of America; Ansari ALS Center for Stem Cell and Regeneration Research at Johns Hopkins, Baltimore, Maryland, 21205, United States of America.
Rita Sattler, Department of Neurology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, 21205, United States of America; Brain Science Institute, Johns Hopkins University, Baltimore, Maryland, 21205, United States of America.
Nicholas J. Maragakis, Department of Neurology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, 21205, United States of America; Ansari ALS Center for Stem Cell and Regeneration Research at Johns Hopkins, Baltimore, Maryland, 21205, United States of America.
Jeffrey D. Rothstein, Department of Neurology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, 21205, United States of America; Brain Science Institute, Johns Hopkins University, Baltimore, Maryland, 21205, United States of America; Department of Neuroscience, Johns Hopkins University, School of Medicine, Baltimore, Maryland, 21205, United States of America.

Document Type

Article

Abstract

Amyotrophic lateral sclerosis is a progressive disease characterized by the loss of upper and lower motor neurons, leading to paralysis of voluntary muscles. About 10% of all ALS cases are familial (fALS), among which 15-20% are linked to Cu/Zn superoxide dismutase (SOD1) mutations, usually inherited in an autosomal dominant manner. To date only one FDA approved drug is available which increases survival moderately. Our understanding of ALS disease mechanisms is largely derived from rodent model studies, however due to the differences between rodents and humans, it is necessary to have humanized models for studies of disease pathogenesis as well as drug development. Therefore, we generated a comprehensive library of a total 22 of fALS patient-specific induced pluripotent stem cell (iPSC) lines. These cells were thoroughly characterized before being deposited into the library. The library of cells includes a variety of C9orf72 mutations, sod1 mutations, FUS, ANG and FIG4 mutations. Certain mutations are represented with more than one line, which allows for studies of variable genetic backgrounds. In addition, these iPSCs can be successfully differentiated to astroglia, a cell type known to play a critical role in ALS disease progression. This library represents a comprehensive resource that can be used for ALS disease modeling and the development of novel therapeutics.

Medical Subject Headings

Adult; Aged; Amyotrophic Lateral Sclerosis (genetics, pathology); Astrocytes (metabolism); C9orf72 Protein; Cell Differentiation; Cells, Cultured; Female; Humans; Induced Pluripotent Stem Cells (physiology); Male; Middle Aged; Mutation; Proteins (genetics); Superoxide Dismutase (genetics); Superoxide Dismutase-1; Tissue Banks

Publication Date

1-1-2015

Publication Title

PloS one

E-ISSN

1932-6203

Volume

10

Issue

3

First Page

e0118266

PubMed ID

25760436

Digital Object Identifier (DOI)

10.1371/journal.pone.0118266

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