The expanding world of stem cell modeling of Huntington's disease: creating tools with a promising future

Jacqueline M Ward,Albert R La Spada

doi:10.1186/gm369

Abstract

Deconstructing the mechanistic basis of neurodegenerative disorders, such as Huntington's disease (HD), has been a particularly challenging undertaking, relying mostly on post-mortem tissue samples, non-neural cell lines from affected individuals, and model organisms. Two articles recently published in Cell Stem Cell report first the generation and characterization of induced pluripotent stem cell (iPSC)-derived models for HD, and second, the genetic correction of a disease-causing CAG expansion mutation in iPSCs from individuals with HD. Taken together, these two studies provide a framework for the production and validation of iPSC materials for human neurodegenerative disease research and yield crucial tools for investigating future therapies.

Highlights

Application of stem cell modeling to Huntington’s disease: the time is Huntington’s disease (HD) is a progressive, autosomal dominantly inherited neurodegenerative disorder, characterized by impaired motor control, cognitive decline, and occasional psychiatric illness
As generation and characterization of induced pluripotent stem cell (iPSC) lines can be laborious and costly, one obvious solution to assure the validity of iPSC disease models is to create research teams that work together on a particular disorder, sharing iPSC lines and derived neurons. is very strategy was applied in the HD iPSC Consortium study [2], in which eight different groups produced iPSCs from three individuals with HD and three control individuals and used them to assay a wide range of phenotypes. ese included gene expression, cell adhesion, bioenergetics, glutamate toxicity, cell death, calcium flux, and trophic factor withdrawal
These phenotypes were assessed in neural stem cells (NSCs) grown in spherical aggregates under defined growth factor conditions, as well as in differentiated striatal-like neurons obtained using both long and short differen tiation protocols, which differed in the growth factors that were added

Summary

Introduction

Application of stem cell modeling to Huntington’s disease: the time is Huntington’s disease (HD) is a progressive, autosomal dominantly inherited neurodegenerative disorder, characterized by impaired motor control, cognitive decline, and occasional psychiatric illness. Is very strategy was applied in the HD iPSC Consortium study [2], in which eight different groups produced iPSCs from three individuals with HD and three control individuals and used them to assay a wide range of phenotypes.

Results

Conclusion