Induced pluripotent stem cells from a spinal muscular atrophy patient.
Spinal muscular atrophy is one of the most common inherited forms of neurological disease leading to infant mortality. Patients have selective loss of lower motor neurons resulting in muscle weakness, paralysis and often death. Although patient fibroblasts have been used extensively to study spinal muscular atrophy, motor neurons have a unique anatomy and physiology which may underlie their vulnerability to the disease process. Here we report the generation of induced pluripotent stem cells from skin fibroblast samples taken from a child with spinal muscular atrophy. These cells expanded robustly in culture, maintained the disease genotype and generated motor neurons that showed selective deficits compared to those derived from the child's unaffected mother. This is the first study to show that human induced pluripotent stem cells can be used to model the specific pathology seen in a genetically inherited disease. As such, it represents a promising resource to study disease mechanisms, screen new drug compounds and develop new therapies.
Ebert
Allison D
AD
The Waisman Center, The Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, 1500 Highland Avenue, Madison, Wisconsin 53705, USA. ebert@waisman.wisc.edu
Yu
Junying
J
Rose
Ferrill F
FF
Mattis
Virginia B
VB
Lorson
Christian L
CL
Thomson
James A
JA
Svendsen
Clive N
CN
D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D002469:Cell Separation; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000187:drug effects; D002648:Child; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D008954:Models, Biological; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009134:Muscular Atrophy, Spinal / Q000378:metabolism / Q000473:pathology*; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D012867:Skin / Q000166:cytology; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics / Q000378:metabolism
D055533:Survival of Motor Neuron 1 Protein