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Modelling Premature Cardiac Aging with Induced Pluripotent Stem Cells From a Hutchinson-Gilford Progeria Syndrome Patient

ABSTRACT: Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic disorder that causes accelerated aging and a high risk of cardiovascular complications. However, the underlying mechanisms of cardiac complications of this syndrome are not fully understood. This study modeled HGPS using cardiomyocytes (CM) derived from induced pluripotent stem cells (iPSC) derived from a patient with HGPS and characterized the biophysical, morphological, and molecular changes found in these CM compared to CM derived from a healthy donor. Electrophysiological recordings revealed that the HGPS CM was functional and had normal electrophysiological properties. Electron tomography showed nuclear morphology alteration and 3D reconstruction of electron tomography images indicated structural abnormalities in HGPS CM mitochondria. High-resolution respirometry with isolated CM derived from three distinct cellular differentiations suggests that HGPS-CM had a tendency of lower oxygen consumption capacity. However, there was no difference in mitochondrial content as measured by Mitotracker. Telomere length was measured using qRT-PCR, and no difference was found in either the iPSCs or the CM from HGPS when compared to the control. Proteomic analysis was carried out in a high-resolution system using Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS). The proteomics data show distinct group separations and protein expression differences between HGPS and control-CM, highlighting changes in ribosomal, TCA cycle, and amino acid biosynthesis, among other modifications. Our findings show that iPSC-derived cardiomyocytes from a Progeria Syndrome patient have significant changes in mitochondrial morphology and protein expression, implying novel mechanisms underlying premature cardiac aging

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Stem Cell, Cell Culture

DISEASE(S): Progeria

SUBMITTER: Gustavo Monnerat

LAB HEAD: Gustavo Monnerat

PROVIDER: PXD036557 | Pride | 2022-11-10

REPOSITORIES: Pride

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Modelling Premature Cardiac Aging with Induced Pluripotent Stem Cells From a Hutchinson-Gilford Progeria Syndrome Patient

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