Table 2.
iPSC-based models of laminopathies.
| Disease | LMNA mutation | iPSC-derived cell type | Phenotypes | References |
|---|---|---|---|---|
| HGPS | G608G | MSCs; VSMCs; FBs; ECs; NPs | FBs,VSMCs, MSCs: high progerin levels, DNA damage, nuclear abnormalities VSMCs, MSCs: Reduced viability induced by stress and hypoxia ECs, NPs: no phenotype | Zhang et al., 2011 |
| HGPS | G608G | FBs | Nuclear blebbing, cellular senescence, slow proliferation, electrical induced apoptosis | Ho et al., 2011 |
| HGPS | G608G | VSMCs; FBs | VSMCs, FBs: nuclear lamina disorganization, loss of heterochromatin VSMCs: premature senescence | Liu et al., 2011a |
| HGPS | G608G | Adipocytes | Severe lipid storage defect at late differentiation stage, PPARγ2 and C/EBPα transcriptional inhibition | Xiong et al., 2013 |
| HGPS | G608G | MSCs | Comparative study evaluating functional effects of the three pharmacological treatments approved for HGPS patients (FTIs, ZoPra, rapamycin) | Blondel et al., 2014 |
| HGPS | G608G | ECs | Cell death due to a sustained [Ca2+]i elevation caused by TRPV2 upregulation | Lo et al., 2014 |
| HGPS | G608G | VSMCs | Progerin induced cell death via PARP1 down-regulation | Zhang et al., 2014 |
| HGPS | G608G | MSCs | Identification of mono-aminopyrimidines (Mono-AP) as potential therapeutic molecule for HGPS | Blondel et al., 2016 |
| HGPS | G608G | 3D-tissue engineered blood vessels | Recapitulation of HGPS phenotypes in 3D setting, drugs testing | Atchison et al., 2017 |
| HGPS | G608G | iPSCs | Genome-wide analysis of HGPS epigenetic landscape in pluripotent cells | Chen et al., 2017 |
| aWS | E578V | FBs | Nuclear blebbing, cellular senescence, slow proliferation, electrical induced apoptosis | Ho et al., 2011 |
| FPLD2 | R482W | Adipocytes | Altered adipogenesis, insulin resistance, increased autophagy | Friesen and Cowan, 2018 |
| FPLD2 | R482W | ECs | Defective early vascular differentiation mediated by T/Brachiury deregulation | Briand et al., 2018 |
| DCM | GCCA insertion | FBs | Nuclear blebbing, cellular senescence, slow proliferation, electrical induced apoptosis | Ho et al., 2011 |
| DCM | R225X; GCCA insertion | CMs | Nuclear abnormalities, ERK1/2-mediated susceptibility to electrical stimulation | Siu et al., 2012 |
| DCM | R225X; Q354X; T518fs frameshift mutation | CMs | R225X-CMs: Improved senescence, apoptosis, excitation-contraction coupling, and contractile functions induced by PTC124 treatment | Lee et al., 2017 |
| DCM | R190W | CMs | Sarcomeric disorganization, abnormal activation of ERK1/2 signaling | Chatzifrangkeskou et al., 2018 |
List of the reported models of laminopathy-related diseases generated through iPSC technology and schematic description of the phenotypes detected in the diverse analyzed cell types. MSCs, mesenchymal stem cells; VSMCs, vascular smooth muscle cells; FBs, fibroblasts; ECs, endothelial cells; NPs, neural progenitors; CMs, cardiomyocytes.