Targeting the histone demethylase LSD1 prevents cardiomyopathy in a mouse model of laminopathy.

LMNA mutations in patients are responsible for a dilated cardiomyopathy. Molecular mechanisms underlying the origin and development of the pathology are unknown. Herein, using mouse pluripotent embryonic stem cells (ESCs) and a mouse model both harboring the p.

Improved Protocol for Cardiac Differentiation and Maturation of Pluripotent Stem Cells.

Pluripotent stem cells feature the capacity to differentiate into any somatic cell types including cardiomyocytes. We report a cost-effective and simple protocol for the differentiation of specific ventricular cardiomyocytes. These cells are elongated, do not spontaneously beat, and do not feature any Ca-transient, an index of their stage of maturation toward adult cardiac cells.

Cofilin-1 phosphorylation catalyzed by ERK1/2 alters cardiac actin dynamics in dilated cardiomyopathy caused by lamin A/C gene mutation.

Hyper-activation of extracellular signal-regulated kinase (ERK) 1/2 contributes to heart dysfunction in cardiomyopathy caused by mutations in the lamin A/C gene (LMNA cardiomyopathy). The mechanism of how this affects cardiac function is unknown. We show that active phosphorylated ERK1/2 directly binds to and catalyzes the phosphorylation of the actin depolymerizing factor cofilin-1 on Thr25.

Epigenetic Regulation of Cardiac Differentiation of Embryonic Stem Cells and Tissues.

Specific gene transcription is a key biological process that underlies cell fate decision during embryonic development. The biological process is mediated by transcription factors which bind genomic regulatory regions including enhancers and promoters of cardiac constitutive genes. DNA is wrapped around histones that are subjected to chemical modifications.