Decay in survival motor neuron and plastin 3 levels during differentiation of iPSC-derived human motor neurons
Por:
Boza-Moran, MG, Martinez-Hernandez, R, Bernal, S, Wanisch, K, Also-Rallo, E, Le Heron, A, Alias, L, Denis, C, Girard, M, Yee, JK, Tizzano, EF, Yanez-Munoz, RJ
Publicada:
26 jun 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.
Filiaciones:
Boza-Moran, MG:
Univ London, Sch Biol Sci, Egham TW20 0EX, Surrey, England
Martinez-Hernandez, R:
Univ London, Sch Biol Sci, Egham TW20 0EX, Surrey, England
Hosp Santa Creu & Sant Pau, Dept Genet, Barcelona, Spain
Hosp Santa Creu & Sant Pau, CIBERER, U 705, Barcelona, Spain
Bernal, S:
Hosp Santa Creu & Sant Pau, Dept Genet, Barcelona, Spain
Hosp Santa Creu & Sant Pau, CIBERER, U 705, Barcelona, Spain
Wanisch, K:
Univ London, Sch Biol Sci, Egham TW20 0EX, Surrey, England
Also-Rallo, E:
Hosp Santa Creu & Sant Pau, Dept Genet, Barcelona, Spain
Hosp Santa Creu & Sant Pau, CIBERER, U 705, Barcelona, Spain
Le Heron, A:
Univ London, Sch Biol Sci, Egham TW20 0EX, Surrey, England
Alias, L:
Hosp Santa Creu & Sant Pau, Dept Genet, Barcelona, Spain
Hosp Santa Creu & Sant Pau, CIBERER, U 705, Barcelona, Spain
Denis, C:
Inst Stem Cell Therapy & Explorat Monogen Dis, Evry, France
Girard, M:
Inst Stem Cell Therapy & Explorat Monogen Dis, Evry, France
Yee, JK:
City Hope Natl Med Ctr, Beckman Res Inst, Dept Virol, Duarte, CA 91010 USA
Tizzano, EF:
Hosp Santa Creu & Sant Pau, Dept Genet, Barcelona, Spain
Hosp Santa Creu & Sant Pau, CIBERER, U 705, Barcelona, Spain
Yanez-Munoz, RJ:
Univ London, Sch Biol Sci, Egham TW20 0EX, Surrey, England
Gold, Green Published
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