Selective Death in Spinal Muscular Atrophy: Genome-Wide RNA-Seq Using Purified Patient-Derived Motor Neurons

ABSTRACT: Spinal Muscular Atrophy (SMA) is well-known to be caused by mutations in the gene Survival of Motor Neuron 1 (SMN1). Because this gene is ubiquitously expressed, it remains poorly understood why motor neurons (MNs) are one of the most affected cell types. To begin to address this question, we carried out RNA-sequencing studies using fixed, antibody-labeled and purified MNs produced from control and SMA patient-derived induced pluripotent stem cells (iPSCs). We found SMA-specific changes in MNs, including hyper-activation of the endoplasmic reticulum (ER) stress pathway and enhanced apoptosis. Functional studies demonstrated that inhibition of ER stress improves overall MN health and survival in vitro even in MNs with low SMN levels. In SMA mice, we show that systemic delivery of an ER stre

ORGANISM(S): Homo sapiens

SUBMITTER: David Hendrickson 

PROVIDER: E-GEOD-69175 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress