Key Features
Enhance your research with our curated data sets and powerful platform features. Pluto Bio makes it simple to find and use the data you need.
Learn MoreHereditary sensory neuropathy type 1 (HSN1) is caused by mutations in either the SPTLC1 or SPTLC2 sub-units of the enzyme Serine Palmitoyl Transferase resulting in the production of Deoxyshingobases (DSBs). Exogenous DSBs are toxic when acutely applied to neurons however its unknown whether endogenous DSBs are neurotoxic and the mechanism of such toxicity. Using induced pleuripotent stem cells (iPSC) from HSN1 patients we found increased DSB production from both hepatocytes and sensory neurons. Gene expression profiling in HSN1 iPSCd-sensory neurons showed dysregulation in axon outgrowth and lipid signalling pathways. We noted reduced lipid raft formation, impaired growth factor signalling and reduced neurite outgrowth in these neurons. Gangliosides which are essential for membrane dynamics and lipid raft formation and were globally reduced due to feedback inhibition of DSBs on the enzyme In co-cultures between HSN1 iPSCd-sensory neurons and rat Schwann the nodal complex and myelin were disrupted. HSN1 SPTLC mutations therefor impair cell autonomous and inter-cellular signalling due to altered lipid metabolism, changes which could largely be prevented by treatment with Serine (which reduces DSB production) supporting Serine as a rational therapy. SOURCE: Georgios Baskozos (georgios.baskozos@ndcn.ox.ac.uk) - Neural Injury Group Oxford University
View on GEOView in PlutoEnhance your research with our curated data sets and powerful platform features. Pluto Bio makes it simple to find and use the data you need.
Learn MoreUse Pluto's intuitive interface to analyze and visualize data for this experiment. Pluto's platform is equipped with an API & SDKs, making it easy to integrate into your internal bioinformatics processes.
Read about post-pipeline analysisView quality control data and experiment metadata for this experiment.
Request imports from GEO or TCGA directly within Pluto Bio.
Chat with our Scientific Insights team