Modelling familial dysautonomia in human induced pluripotent stem cells

Gabsang Lee, Lorenz Studer

Research output: Contribution to journalArticle

Abstract

Induced pluripotent stem (iPS) cells have considerable promise as a novel tool for modelling human disease and for drug discovery. While the generation of disease-specific iPS cells has become routine, realizing the potential of iPS cells in disease modelling poses challenges at multiple fronts. Such challenges include selecting a suitable disease target, directing the fate of iPS cells into symptom-relevant cell populations, identifying disease-related phenotypes and showing reversibility of such phenotypes using genetic or pharmacological approaches. Finally, the system needs to be scalable for use in modern drug discovery. Here, we will discuss these points in the context of modelling familial dysautonomia (FD, Riley-Day syndrome, hereditary sensory and autonomic neuropathy III (HSAN-III)), a rare genetic disorder in the peripheral nervous system. We have demonstrated three disease-specific phenotypes in FD-iPS-derived cells that can be partially rescued by treating cells with the plant hormone kinetin. Here, we will discuss how to use FDiPS cells further in high throughput drug discovery assays, in modelling disease severity and in performing mechanistic studies aimed at understanding disease pathogenesis. FD is a rare disease but represents an important testing ground for exploring the potential of iPS cell technology in modelling and treating human disease.

Original languageEnglish (US)
Pages (from-to)2286-2296
Number of pages11
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Volume366
Issue number1575
DOIs
StatePublished - Jul 4 2011
Externally publishedYes

Fingerprint

Familial Dysautonomia
dysautonomia
Induced Pluripotent Stem Cells
Stem cells
stem
modeling
human diseases
phenotype
drugs
Drug Discovery
drug
cells
peripheral nervous system
peripheral nervous system diseases
Phenotype
genetic disorders
kinetin
plant hormones
disease severity
signs and symptoms (animals and humans)

Keywords

  • Disease modelling
  • Drug discovery
  • Human genetic disease
  • Human induced pluripotent stem cells
  • Peripheral nervous system
  • Stem cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Modelling familial dysautonomia in human induced pluripotent stem cells. / Lee, Gabsang; Studer, Lorenz.

In: Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 366, No. 1575, 04.07.2011, p. 2286-2296.

Research output: Contribution to journalArticle

@article{c283466432514948a7c2286a774a27bc,
title = "Modelling familial dysautonomia in human induced pluripotent stem cells",
abstract = "Induced pluripotent stem (iPS) cells have considerable promise as a novel tool for modelling human disease and for drug discovery. While the generation of disease-specific iPS cells has become routine, realizing the potential of iPS cells in disease modelling poses challenges at multiple fronts. Such challenges include selecting a suitable disease target, directing the fate of iPS cells into symptom-relevant cell populations, identifying disease-related phenotypes and showing reversibility of such phenotypes using genetic or pharmacological approaches. Finally, the system needs to be scalable for use in modern drug discovery. Here, we will discuss these points in the context of modelling familial dysautonomia (FD, Riley-Day syndrome, hereditary sensory and autonomic neuropathy III (HSAN-III)), a rare genetic disorder in the peripheral nervous system. We have demonstrated three disease-specific phenotypes in FD-iPS-derived cells that can be partially rescued by treating cells with the plant hormone kinetin. Here, we will discuss how to use FDiPS cells further in high throughput drug discovery assays, in modelling disease severity and in performing mechanistic studies aimed at understanding disease pathogenesis. FD is a rare disease but represents an important testing ground for exploring the potential of iPS cell technology in modelling and treating human disease.",
keywords = "Disease modelling, Drug discovery, Human genetic disease, Human induced pluripotent stem cells, Peripheral nervous system, Stem cells",
author = "Gabsang Lee and Lorenz Studer",
year = "2011",
month = "7",
day = "4",
doi = "10.1098/rstb.2011.0026",
language = "English (US)",
volume = "366",
pages = "2286--2296",
journal = "Philosophical Transactions of the Royal Society B: Biological Sciences",
issn = "0800-4622",
publisher = "Royal Society of London",
number = "1575",

}

TY - JOUR

T1 - Modelling familial dysautonomia in human induced pluripotent stem cells

AU - Lee, Gabsang

AU - Studer, Lorenz

PY - 2011/7/4

Y1 - 2011/7/4

N2 - Induced pluripotent stem (iPS) cells have considerable promise as a novel tool for modelling human disease and for drug discovery. While the generation of disease-specific iPS cells has become routine, realizing the potential of iPS cells in disease modelling poses challenges at multiple fronts. Such challenges include selecting a suitable disease target, directing the fate of iPS cells into symptom-relevant cell populations, identifying disease-related phenotypes and showing reversibility of such phenotypes using genetic or pharmacological approaches. Finally, the system needs to be scalable for use in modern drug discovery. Here, we will discuss these points in the context of modelling familial dysautonomia (FD, Riley-Day syndrome, hereditary sensory and autonomic neuropathy III (HSAN-III)), a rare genetic disorder in the peripheral nervous system. We have demonstrated three disease-specific phenotypes in FD-iPS-derived cells that can be partially rescued by treating cells with the plant hormone kinetin. Here, we will discuss how to use FDiPS cells further in high throughput drug discovery assays, in modelling disease severity and in performing mechanistic studies aimed at understanding disease pathogenesis. FD is a rare disease but represents an important testing ground for exploring the potential of iPS cell technology in modelling and treating human disease.

AB - Induced pluripotent stem (iPS) cells have considerable promise as a novel tool for modelling human disease and for drug discovery. While the generation of disease-specific iPS cells has become routine, realizing the potential of iPS cells in disease modelling poses challenges at multiple fronts. Such challenges include selecting a suitable disease target, directing the fate of iPS cells into symptom-relevant cell populations, identifying disease-related phenotypes and showing reversibility of such phenotypes using genetic or pharmacological approaches. Finally, the system needs to be scalable for use in modern drug discovery. Here, we will discuss these points in the context of modelling familial dysautonomia (FD, Riley-Day syndrome, hereditary sensory and autonomic neuropathy III (HSAN-III)), a rare genetic disorder in the peripheral nervous system. We have demonstrated three disease-specific phenotypes in FD-iPS-derived cells that can be partially rescued by treating cells with the plant hormone kinetin. Here, we will discuss how to use FDiPS cells further in high throughput drug discovery assays, in modelling disease severity and in performing mechanistic studies aimed at understanding disease pathogenesis. FD is a rare disease but represents an important testing ground for exploring the potential of iPS cell technology in modelling and treating human disease.

KW - Disease modelling

KW - Drug discovery

KW - Human genetic disease

KW - Human induced pluripotent stem cells

KW - Peripheral nervous system

KW - Stem cells

UR - http://www.scopus.com/inward/record.url?scp=79960060773&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960060773&partnerID=8YFLogxK

U2 - 10.1098/rstb.2011.0026

DO - 10.1098/rstb.2011.0026

M3 - Article

C2 - 21727134

AN - SCOPUS:79960060773

VL - 366

SP - 2286

EP - 2296

JO - Philosophical Transactions of the Royal Society B: Biological Sciences

JF - Philosophical Transactions of the Royal Society B: Biological Sciences

SN - 0800-4622

IS - 1575

ER -