Patient-specific iPSC-derived cardiomyocytes display key features of ARVC, including reduced cell surface localization of desmosomal proteins and a more adipogenic phenotype.

The emergence of induced pluripotent stem cell (iPSC) technology has had a great impact on the field of medicine ever since the ground-breaking discovery in 2006 that overexpression of four specific transcription factors was able to turn back the developmental clock of somatic cells into an embryonic-like state. The resulting iPSCs carry the developmental potential of human embryonic stem cells (hESC) without the embryo and have been heralded as a powerful tool to study development and disease. This technology has made it possible for the first time for researchers to transform end-differentiated cells from a particular individual into another cell type that remains specific to that individual, paving the way for novel methods of in vitro disease modelling and therapeutic applications. This paper reviews some of the key areas in cardiovascular medicine in which iPSC technology has been applied and discusses the future directions and ongoing challenges ahead in this exciting field.

Pin1 is a peptidyl-prolyl cis-trans isomerase which catalyzes the isomerization of phosphorylated Ser/Thr-Pro peptide bonds. Pin1 knockout mice have marked abnormalities in their reproductive development and function. However, the molecular mechanisms underlying their reproductive defects are poorly understood. Herein, we demonstrate that Pin1 is required for both basal and GnRH-induced gonadotropin ␤-subunit gene transcription, through interactions with the transcription factors SF-1, Pitx1, and Egr-1. Pin1 activates transcription of the gonadotropin ␤-subunit genes synergistically with these transcription factors, either by modulating their stability or by increasing their protein-protein interactions. Notably, we provide evidence that Pin1 is required for the Ser203 phosphorylation-dependent ubiquitination of SF-1, which facilitates SF-1-Pitx1 interactions and therefore results in an enhancement of SF-1 transcriptional activity. Furthermore, we demonstrate that in gonadotrope cells, sufficient levels of activated Pin1 are maintained through transcriptional and posttranslational regulation by GnRH-induced signaling cascades. Our results suggest that Pin1 functions as a novel player in GnRH-induced signal pathways and is involved in gonadotropin ␤-subunit gene transcription by modulating the activity of various specific transcription factors.

Pin1 is a peptidyl‐prolyl cis/trans isomerase which catalyzes the isomerisation of phosphorylated Ser/Thr‐Pro peptide bonds. Pin1 knock‐out mice have a phenotype showing marked abnormalities in their reproductive development and function. However, the molecular mechanisms underlying their reproductive defects are poorly understood. We demonstrate here that Pin1 is required for the basal and GnRH‐induced gonadotropin β‐subunit gene transcription. Knocking down Pin1 expression by small interfering RNA (siRNA) reduces both gonadotropin β‐subunit gene promoter activity and endogenous mRNA levels. In addition, co‐immunoprecipitations and mammalian two hybrid assays show that Pin1 interacts with the transcription factors, SF‐1, Pitx1 and Egr‐1. Pin1 activates transcription of the gonadotropin β‐subunit genes synergistically with these transcription factors, either by modulating their stability or through increasing their protein‐protein interactions. Our results suggest that Pin1 functions as a novel player in GnRH‐induced signal pathway, involved in gonadotropin β‐subunit gene transcription by modulating the activity of various specific transcription factors.