Decay in survival motor neuron and plastin 3 levels during differentiation of iPSC-derived human motor neurons

作者：Boza Moran Maria G; Martinez Hernandez Rebeca; Bernal Sara; Wanisch Klaus; Also Rallo Eva; Le Heron Anita; Alias Laura; Denis Cecile; Girard Mathilde; Yee Jiing Kuan; Tizzano Eduardo F; Yanez Munoz Rafael J^*

来源：Scientific Reports, 2015, 5(1): 11696.

DOI：10.1038/srep11696

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.

• 出版日期2015-6-26