Transcriptomics

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Regulation of PERK-eIF2α Signaling by Tuberous Sclerosis Complex-1 Controls Homeostasis and Survival of Myelinating Oligodendrocytes


ABSTRACT: Tuberous sclerosis complex (TSC), an autosomal dominant disorder caused by mutations in either TSC1 or TSC2, exhibits white matter abnormalities including CNS myelin deficits. however, underlying mechanisms are not fully understood. Here we find that, unexpectedly, constitutive activation of mTOR signaling caused by Tsc1 deletion in the oligodendrocyte lineage results in severe myelination defects and oligodendrocyte cell death. Expression profiling analysis reveals that Tsc1 ablation induces prominent endoplasmic reticulum (ER) stress responses through the PERK‐eIF2α dependent signaling axis and activates Fas-JNK apoptotic pathways. Our studies suggest that TSC1-mTOR signaling acts as an important checkpoint for maintaining oligodendrocyte homeostasis.

ORGANISM(S): Mus musculus

PROVIDER: GSE74893 | GEO | 2016/07/22

SECONDARY ACCESSION(S): PRJNA301738

REPOSITORIES: GEO

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