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Phenotypic Rescue of Induced Pluripotent Stem Cell-Derived Motoneurons of a Spinal Muscular Atrophy Patient.
MedLine Citation:
PMID:  21956898     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Spinal muscular atrophy (SMA) is one of the most common autosomal recessive disorders in humans and a common genetic cause of infant mortality. The disease is caused by loss of the survival of motoneuron (SMN) protein, resulting in the degeneration of alpha motoneurons in spinal cord and muscular atrophy in the limbs and trunk. One function of SMN involves RNA splicing. It is unclear why a deficiency in a housekeeping function such as RNA splicing only causes profound effects on motoneurons but not on other cell types. One difficulty in studying SMA is the scarcity of patient's samples. The discovery that somatic cells can be reprogrammed to become induced pluripotent stem (iPS) cells raises the intriguing possibility of modeling human diseases in vitro. We reported the establishment of five iPS cell lines from the fibroblasts of a type 1 SMA patient. Neuronal cultures derived from these SMA iPS cell lines exhibited a reduced capacity to form motoneurons and an abnormality in neurite outgrowth. Ectopic SMN expression in these iPS cell lines restored normal motoneuron differentiation and rescued the phenotype of delayed neurite outgrowth. These results suggest that the observed abnormalities are indeed caused by SMN deficiency and not by iPS cell clonal variability. Further characterization of the cellular and functional deficits in motoneurons derived from these iPS cells may accelerate the exploration of the underlying mechanisms of SMA pathogenesis.
Authors:
Tammy Chang; Weiyan Zheng; Walter Tsark; Steven E Bates; He Huang; Ren-Jang Lin; Jiing-Kuan Yee
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-28
Journal Detail:
Title:  Stem cells (Dayton, Ohio)     Volume:  -     ISSN:  1549-4918     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9304532     Medline TA:  Stem Cells     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 AlphaMed Press.
Affiliation:
Department of Virology, Beckman Research Institute, City of Hope, Duarte, CA, USA.
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