Decay in survival motor neuron and plastin 3 levels during differentiation of iPSC-derived human motor neurons
Boza-Morán, María G. (University of London)
Martínez-Hernández, Rebeca (Institut d'Investigació Biomèdica Sant Pau)
Bernal, Sara (Institut d'Investigació Biomèdica Sant Pau)
Wanisch, Klaus (University of London)
Also-Rallo, Eva (Institut d'Investigació Biomèdica Sant Pau)
Le Heron, Anita (University of London)
Alías, Laura (Institut d'Investigació Biomèdica Sant Pau)
Denis, Cécile (Institute for Stem Cell Therapy and Exploration of Monogenic Diseases)
Girard, Mathilde (Institute for Stem Cell Therapy and Exploration of Monogenic Diseases)
Yee, Jiing-Kuan (Beckman Research Institute)
Tizzano, Eduardo F. (Hospital Universitari Vall d'Hebron)
Yáñez-Muñoz, Rafael J (University of London)
Universitat Autònoma de Barcelona

Fecha:	2015
Resumen:	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.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Animals ; Biomarkers ; Cell Differentiation ; Cell Survival ; Clone Cells ; Coculture Techniques ; Female ; Humans ; Induced Pluripotent Stem Cells ; Male ; Membrane Glycoproteins ; Mice ; Microfilament Proteins ; Motor Neurons ; Muscle Fibers, Skeletal ; Neurites ; Pedigree ; Survival of Motor Neuron 1 Protein
Publicado en:	Scientific reports, Vol. 5 (26 2015) , p. 11696, ISSN 2045-2322

DOI: 10.1038/srep11696
PMID: 26114395

17 p, 2.8 MB

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