Proteomic Insights Into Spinal Muscular Atrophy using Patient-Derived Motor Neurons and Hepatocytes
Description
Spinal Muscular Atrophy (SMA) is classically defined by motor neuron loss but increasing evidence points to broader systemic involvement including the liver. We investigated shared and tissue-specific molecular differences in liver and motor neurons to understand systemic effects of SMA in SMA patients and carriers. Using patient-derived stem cells from SMA patients and control, we generated induced liver (iHeps) and motor neuron (iMNs) cells. We further created isogenic carrier and wild-type lines from the same SMA patient using genome editing. Commonly dysregulated proteins in SMA lines in iHeps and iMNs were upregulated in cell structure and extracellular matrix organization; and downregulated in mitochondrial function and metabolism-related processes. Among them, 36 proteins showed SMN-dependent effects and were involved in protein hydroxylation, tissue organization, wound healing and cell adhesion. Proteins dysregulated in isogenic carriers were largely tissue-specific and involved in immune function, metabolism and intracellular transport, with five proteins showing cross-tissue dysregulation. Our findings reinforce SMA’s multi-system nature, even in asymptomatic carriers Here, we upload the unprocessed data from ProteomeDiscoverer search results from the paper. Data 1 - All 15 iMNs samples (3 replicates of 1-38G, 1-51N, GM23720, HOM and HET) Data 2 - 15 iHeps SMA and WT samples (9 replicates of 1-38G, 3 replicates of 1-51N and GM23720) Data 3 - 27 iHeps isogenic samples (split into 3 TMT sets of 3 replicates of 1-38G, HOM and HET each)