Mutations in the retinoblastoma tumor suppressor gene Rb are involved in many forms of human cancer. In this study, we investigated the early consequences of inactivating Rb in the context of cellular reprogramming. We found that Rb inactivation promotes the reprogramming of differentiated cells to a pluripotent state. Unexpectedly, this effect is cell cycle independent, and instead reflects di...

Cohesin is implicated in establishing and maintaining pluripotency. Whether this is because of essential cohesin functions in the cell cycle or in gene regulation is unknown. Here we tested cohesin's contribution to reprogramming in systems that reactivate the expression of pluripotency genes in the absence of proliferation (embryonic stem [ES] cell heterokaryons) or DNA replication (nuclear tr...

Mammalian parthenogenetic embryos (pE) are not viable due to placental deficiency, presumably resulting from lack of paternally expressed imprinted genes. Pluripotent parthenogenetic embryonic stem (pES) cells derived from pE could advance regenerative medicine by avoiding immuno-rejection and ethical roadblocks. We attempted to explore the epigenetic status of imprinted genes in the generation...

Arrhythmogenic Cardiomyopathy (ACM) is a rare genetic cardiac disease predominantly associated with mutations in genes of the desmosomes and characterized by arrhythmia fibro-fatty replacement myocardium. We generated human induced pluripotent stem cells (hiPSCs) from one patient affected ACM carrying heterozygous c.1643delG (p.G548VfsX15) PKP2 mutation then corrected using CRISPR/Cas9 technolo...

Pluripotency confers Embryonic Stem Cells (ESCs) the ability to differentiate in ectoderm, endoderm, and mesoderm derivatives, producing the majority of cell types. Although the majority of ESCs divide without losing pluripotency, it has become evident that ESCs culture consists of multiple cell populations with different degrees of potency that are spontaneously induced in regular ESC culture ...

The canonical Wnt pathway is critical for embryonic stem cell (ESC) pluripotency and aberrant control of β-catenin leads to failure of exit from pluripotency and lineage commitments. Hence, maintaining the appropriate level of β-catenin is important for the decision to commit to the appropriate lineage. However, how β-catenin links to core transcription factors in ESCs remains elusive. C-termin...

Arrhythmogenic cardiomyopathy (ACM) is characterized by fibro-fatty replacement of the myocardium, heart failure and life-threatening ventricular arrhythmias. Causal mutations were identified in genes encoding for proteins desmosomes, predominantly plakophilin-2 (PKP2) desmoglein-2 (DSG2). We generated gene-edited knock-out iPSC lines PKP2 (JMUi001-A-2) DSG2 (JMUi001-A-3) using CRISPR/Cas9 syst...

Inadequate silencing of exogenous genes represents a major obstacle to complete epigenetic reprogramming of porcine-induced pluripotent stem cells (piPSCs) by conventional pluripotency transcription factors (OSKM). We tested the hypothesis that epigenetic modification by active DNA or histone demethylation or by inhibition of histone deacetylase would enhance reprogramming and exogenous gene si...

Left Ventricular Noncompaction Cardiomyopathy (LVNC) is characterized by excessive trabeculation of the left ventricle. To date, mutations in more than 40 genes have been associated with LVNC, however exact mechanisms underlying disease remain unknown. Here, we describe an induced pluripotent stem cell (iPSC) line (UALGi001-A) from a LVNC patient (LVNC-iPSC) that does not present most commonly ...

Prostate Cancer (PCa)-related deaths are mostly due to metastasization of poorly differentiated adenocarcinomas often endowed with neuroendocrine differentiation (NED) areas.The SNAI2/Slug gene is a major regulator of cell migration and tumor metastasization. We here assessed its biological significance in NED, and metastatic potential of PCa.SNAI2 expression was down-regulated in most PCa epit...