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Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can self‐renew indefinitely and contribute to all tissue types of the adult organism. Stem cell‐based therapeutic approaches hold enormous promise for the cure of regenerative diseases. Over the last few years, several studies have attempted to decipher the important role of transcription factor networks and epigenetic regulatory...
Parental effects are a major source of phenotypic plasticity and may influence offspring phenotype in concert with environmental demands. Studies of “environmental epigenetics” suggest that (1) DNA methylation states are variable and that both demethylation and remethylation occur in post‐mitotic cells, and (2) that remodeling of DNA methylation can occur in response to environmentally driven intracellular...
Claudins serve essential roles in regulating paracellular permeability properties within occluding junctions. Recent studies have begun to elucidate developmental roles of claudins within immature tissues. This work has uncovered an involvement of several claudins in determining tight junction properties that have an effect on embryonic morphogenesis and physiology. During zebrafish brain morphogenesis,...
Recent results confirm that long‐term expression of therapeutic transgenes can be achieved by using a transposon‐based system in primary stem cells and in vivo. Transposable elements are natural DNA transfer vehicles that are capable of efficient genomic insertion. The latest generation, Sleeping Beauty transposon‐based hyperactive vector (SB100X), is able to address the basic problem of non‐viral...
Essentially we show recent data to shed new light on the thorny controversy of how teeth arose in evolution. Essentially we show (a) how teeth can form equally from any epithelium, be it endoderm, ectoderm or a combination of the two and (b) that the gene expression programs of oral versus pharyngeal teeth are remarkably similar. Classic theories suggest that (i) skin denticles evolved first and odontode‐inductive...
Cell therapy means treating diseases with the body's own cells. One of the cell types most in demand for therapeutic purposes is the pancreatic β‐cell. This is because diabetes is one of the major healthcare problems in the world. Diabetes can be treated by islet transplantation but the major limitation is the shortage of organ donors. To overcome the shortfall in donors, alternative sources of pancreatic...
Conserved upstream open reading frames (uORFs) are found within many eukaryotic transcripts and are known to regulate protein translation. Evidence from genetic and bioinformatic studies implicates disturbed uORF‐mediated translational control in the etiology of human diseases. A genetic mouse model has recently provided proof‐of‐principle support for the physiological relevance of uORF‐mediated translational...
In eukaryotic cells terminally misfolded proteins of the secretory pathway are retarded in the endoplasmic reticulum (ER) and subsequently degraded in a ubiquitin‐proteasome‐dependent manner. This highly conserved process termed ER‐associated protein degradation (ERAD) ensures homeostasis in the secretory pathway by disposing faulty polypeptides and preventing their deleterious accumulation and eventual...
The emergence of individuality during the evolutionary transition from single cells to multicellularity poses a range of problems. A key issue is how variation in lower‐level individuals generates a corporate (collective) entity with Darwinian characteristics. Of central importance to this process is the evolution of a means of collective reproduction, however, the evolution of a means of collective...
Cancer cells accumulate widespread local and global chromatin changes and the source of this instability remains a key question. Here we hypothesize that chromatin alterations including unscheduled silencing can arise as a consequence of perturbed histone dynamics in response to replication stress. Chromatin organization is transiently disrupted during DNA replication and maintenance of epigenetic...
Modern cells present no signs of a putative prebiotic RNA world. However, RNA coding is not a sine qua non for the accumulation of catalytic polypeptides. Thus, cellular proteins spontaneously fold into active structures that are resistant to proteolysis. The law of mass action suggests that binding domains are stabilized by specific interactions with their substrates. Random polypeptide synthesis...
Small non‐coding RNAs (microRNAs or miRs) represent one of the most fertile areas of cancer research and recent advances in the field have prompted us to reconsider the traditional concept of cancer. Some miRs exert negative control over the expression of numerous oncoproteins in normal cells and consequently their deregulation is believed to be an important mechanism underlying cancer development...
This article proposes that cancers can be initiated by retrotransposon (RTN) activation through changes in the transcriptional regulation of nearby genes. I first detail the hypothesis and then discuss the nature of physiological stress(es) in RTN activation; the role of DNA demethylation in the initiation and propagation of new RTN states; the connection between ageing and cancer incidence and the...
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