Non Animal Testing Database

Single cell transcriptomics to reveal pathological pathways in ALS

November 2021
University of Exeter, Exeter, United Kingdom
Amyotrophic lateral sclerosis is a neurodegenerative disease driven by the loss of motor neurones. Here SOD1 E100G amyotrophic lateral sclerosis patient-derived induced pluripotent stem cells were used to perform single-cell transcriptomics analysis to identify signalling pathways related to the pathological outcome in dysfunctional neurones. The results showed several pathways and transcriptional factors leading to gene expression dysregulation, building an ALS-relevant transcriptional network map. SMAD2, a downstream effector of TGF-beta, was elucidated as a critical factor in SOD motor neurone degeneration. Moreover, TGF-beta was activated in different variations of amyotrophic lateral sclerosis, both familiar and sporadic cases. According to these findings, inhibition of TGF-beta improved diseased SOD1 motor neurone survival. Overall, the researchers demonstrate the utility of single-cell transcriptomics to uncover pathological pathways in neurodegenerative diseases, and this allows them to identify several SOD1-associated targets in perturbed motor neurone transcriptional networks.
Single-cell transcriptomics identifies master regulators of neurodegeneration in SOD1 ALS iPSC-derived motor neurons
Akshay Bhinge
Added on: 11-29-2021
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