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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.

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Figure 1: Newly generated iPS cells were fully reprogrammed.
Figure 2: iPS-SMA cells show decreased SMN transcripts.
Figure 3: iPS-WT and iPS-SMA cells can generate cells in the neural lineage.
Figure 4: iPS-WT and iPS-SMA cells increase SMN protein in response to drug treatment.

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Gene Expression Omnibus

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Microarray data have been deposited in GEO under accession number GSE13828.


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We thank J. Meyer for helpful discussions and B. Shelley, B. Heins and E. McMillan for technical assistance. We also thank WiCell Research Institute for karyotype analysis, Cell Line Genetics for DNA fingerprinting, R. Stewart, S. Tian and V. Ruotti at the Morgridge Institute for Research for microarray analysis, and Promega Corp. for qRT–PCR analysis (all at Madison, Wisconsin). The MNR2/HB9 (81.5C10) and the ISLET1 (40.2D6) monoclonal antibodies (both developed by T. Jessell) were obtained from the Developmental Studies Hybridoma Bank. Funding support was provided by the Amyotrophic Lateral Sclerosis Association (to C.N.S.), the National Institutes of Neurological Disorders and Stroke (P01NS057778 to C.N.S. and R01NS41584 to C.L.L.), National Institutes of Child Health and Human Development (R01HD054413 to C.L.L.), and National Institutes of General Medical Sciences (T32GM008396 for F.F.R.).

Author Contributions A.D.E. participated in all aspects and prepared the manuscript; J.Y. generated and aided in the characterization of iPS-SMA and iPS-WT clones; F.F.R., V.B.M. and C.L.L. performed SMN analysis and manuscript preparation; J.A.T. participated in the generation of the iPS clones; C.N.S. conceived the project and participated in planning, data analysis and manuscript preparation.

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Correspondence to Allison D. Ebert or Clive N. Svendsen.

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Ebert, A., Yu, J., Rose, F. et al. Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature 457, 277–280 (2009).

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