Decay in survival motor neuron and plastin 3 levels during differentiation of iPSC-derived human motor neurons
| Autor: | Maria Gabriela Boza-Morán, Sara Bernal, Klaus Wanisch, Eduardo F. Tizzano, Rafael J. Yáñez-Muñoz, Anita Le Heron, Eva Also-Rallo, Jiing-Kuan Yee, Laura Alias, Mathilde Girard, Cécile V. Denis, Rebeca Martínez-Hernández |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Cell type Neurite Cell Survival Cellular differentiation Induced Pluripotent Stem Cells Muscle Fibers Skeletal SMN1 Biology Article Mice medicine Neurites Animals Humans Induced pluripotent stem cell Genetics Motor Neurons Multidisciplinary Membrane Glycoproteins Microfilament Proteins Cell Differentiation Spinal muscular atrophy Motor neuron medicine.disease SMA Survival of Motor Neuron 1 Protein Coculture Techniques Clone Cells Pedigree medicine.anatomical_structure Female Neuroscience Biomarkers |
| Zdroj: | Scientific Reports r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname |
| ISSN: | 2045-2322 |
| Popis: | Spinal muscular atrophy (SMA) is a neuromuscular disease caused by mutations in Survival Motor Neuron 1 (SMN1), leading to degeneration of alpha motor neurons (MNs) but also affecting other cell types. Induced pluripotent stem cell (iPSC)-derived human MN models from severe SMA patients have shown relevant phenotypes. We have produced and fully characterized iPSCs from members of a discordant consanguineous family with chronic SMA. We differentiated the iPSC clones into ISL-1+/ChAT+ MNs and performed a comparative study during the differentiation process, observing significant differences in neurite length and number between family members. Analyses of samples from wild-type, severe SMA type I and the type IIIa/IV family showed a progressive decay in SMN protein levels during iPSC-MN differentiation, recapitulating previous observations in developmental studies. PLS3 underwent parallel reductions at both the transcriptional and translational levels. The underlying, progressive developmental decay in SMN and PLS3 levels may lead to the increased vulnerability of MNs in SMA disease. Measurements of SMN and PLS3 transcript and protein levels in iPSC-derived MNs show limited value as SMA biomarkers. |
| Databáze: | OpenAIRE |
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