Transdifferentiation involves metamorphosis. The differentiated cells of a particular cotyledon are transformed into the cells of another cotyledon by processes such as histone deacetylation and methylation. Defective processes of transdifferentiation underlie many diseases, such as Barrett’s esthrophagus.
What is transdifferentiation?
Scientists associate transdifferentiation ability primarily with human stem cells. Embryonic development occurs on the basis of three distinct germ layers. Differentiation is a step in embryonic cell development. Cells transform into a specialized form through differentiation processes. The first differentiation of the omnipotent embryonic cells corresponds to the development of the cotyledons, which are tissue-specific and therefore no longer omnipotent. Transdifferentiation is a special case or even a reversion of differentiation. The process corresponds to a metamorphosis. In this process, the cells of one cotyledon are transformed into the cells of another cotyledon. Most transdifferentiation does not occur directly, but corresponds to dedifferentiation, which in turn is followed by differentiation in the opposite directions in each case. Scientists associate transdifferentiation ability primarily with human stem cells. With each transdifferentiation, a complete change of the respective gene expression occurs on the molecular biological level. Each transdifferentiation requires a change of activity in thousands of single gene segments. In connection with some diseases, pathological transdifferentiation processes take place. Basically, however, transdifferentiation need not have any pathological value.
Function and task
During transdifferentiation, the gene expression of a cell changes completely at the molecular genetic level. This has implications for replication. In the transdifferentiated cell, entirely different sections of the gene are replicated than originally intended. For this reason, protein synthesis ends up being completely different from what was originally planned. Transdifferentiation is accompanied by the silencing of previously active genes. This silencing takes place to a large extent through histone deacetylation or methylation processes at the individual DNA segments. The complete course of a transdifferentiation requires an activity change of innumerable sections of a gene. The gene expression of the transdifferentiated cell usually does not correspond in essential parts to the original pattern of gene expression. The process of histone deacetylation not only serves to silence certain gene segments, but also alters the binding ability of DNA. The histone deacetylation process centers on histone, from whose structure an acetyl group is removed. This gives histone a much higher affinity for DNA phosphate groups. This simultaneously results in a lower binding ability between transcription factors and DNA. Transcription factors influence transcription either positively or negatively and are thus either activators or repressors. The reduced binding ability of the transcription factors results in an inhibition of the individual gene expressions located at the corresponding point of the DNA. The process of methylation also ultimately follows the principle of DNA inactivation. The only difference is that in methylation processes, the focus is not on histone but on methyl groups. These methyl groups bind to a specific section of DNA and in this way inactivate the individual DNA sections. During the differentiation of cells, their gene expression changes significantly and many of the genes are even switched off during the processes. Complete transdifferentiation simultaneously relies on high expression of thousands of genes and requires down-regulation in the expression of thousands of other genes at the same time. Only in this way are the right proteins ultimately available for the transformation of the cell. For example, a muscle cell requires fundamentally different proteins than a liver cell. Either transdifferentiation occurs directly or by a detour. This detour corresponds to a dedifferentiation followed by a subsequent redifferentiation in other directions.
Diseases and ailments
Transdifferentiation can underlie many different diseases, making it clinically relevant. For example, the so-called Barrett’s esophagus is associated with the processes of transdifferentiation. This disease is based on a transformation of cells of the epithelium, which are transdifferentiated to mucin-producing intestinal cells during the pathological processes. In this context, there is talk of intestinal metaplasia, which is associated with a facultative risk of degeneration and may favor, for example, the development of adenocarcinomas. In general, Barrett’s syndrome is described as a chronic inflammatory change in the distal esophagus that results in the formation of peptic ulcers, as may occur in the setting of complications of reflux disease. In the syndrome, transformation of squamous epithelium occurs in the distal esophagus. Another disease based on transdifferentiation corresponds to the formation of leukoplakia. Oral mucosal cells transdifferentiate into precancerous cells as part of this phenomenon, which can promote squamous cell carcinoma. Leukoplakia are hyperkeratoses of the mucosa that are often dysplastic at the same time. In addition to the oral cavity, these leukoplakias occur mainly on the lips and in the genital area. Leukoplakia is usually preceded by chronic irritation of the skin or mucous membranes. This irritation thickens the horny layer in the affected area. The reddish mucosa thus turns whitish, as the capillary vessels can no longer be made out under the thick epithelium. The causative stimulus may be mechanical, biological, physical, or chemical. Biological stimuli include chronic viral infections. The chemical causative stimuli are usually caused by smoking or chewing tobacco. Mechanical causative stimuli may include ill-fitting dentures.
