Stem cell differentiation: genome hotspots
New about the development of stem cells
NanoNewsNet by materials Phys.org: New insight into stem cell development
Stem cells are able to differentiate into different types of specialized cells with specific functions. In adult organisms, these cells play an important role in tissue regeneration, and this potential ability can be used to control many diseases, for example, Parkinson's disease or diabetes, the cause of which is the death of specialized cells. Various types of specialized cells can be obtained from a stem cell, but this requires knowledge of the processes that regulate its development.
Scientists from the University of Southern Denmark (University of Southern Denmark) report a new discovery that deepens the understanding of the basic mechanisms of stem cell differentiation, which can accelerate the development of new methods for reprogramming them into exactly the type of cells that a doctor needs to treat a particular disease.
The researchers found that when a stem cell differentiates into a certain type of cell, when reprogramming the DNA chain, proteins called transcription factors work together. A complex, previously unknown interaction is carried out between them.
"Until now, it was believed that only a few transcription factors were responsible for reprogramming, but this is not the case," explains Susanne Mandrup, professor of the Department of Biochemistry and Molecular Biology, head of the study.
"At certain parts of the DNA of the cell, which we call "hot spots", an incredibly complex and hitherto unknown interaction between transcription factors takes place. For the development of stem cells, this interaction in "hot spots" seems to be of great importance. Therefore, in order to better understand the mechanisms controlling this process, it will be very important to study these "hot spots" and the interaction between transcription factors at these sites," the first author of two articles published in the journal Cell Reports clarifies the picture (Transcription Factor Cooperation in Early Adipogenic Hotspots and Super–Enhancers and Molecular Architecture of Transcription Factor Hotspots in Early Adipogenesis) postdoctoral fellow Rasmus Siersbaek. "When we understand these mechanisms, we will have much more effective means to get stem cells to develop in the direction we need."
Obviously, the "hot spots" discovered by Danish scientists are the key nodes of the genome, in which various signals are integrated on a small section of DNA.
The researchers made this discovery by studying how stem cells differentiate into adipose tissue cells. They worked with a well-known line, whose cells can be differentiated into adipocytes (fat cells) in about a week using a certain set of hormones.
Danish scientists have identified 12,000 "hot spots" of transcription factors at an early stage of adipogenesis and found evidence of both simultaneous and sequential binding of transcription factors in these areas.
They showed that large super-enhancer sites (several thousand pairs of nucleotides) inducing early adipogenic reprogramming of gene expression are very rich in hot spots.
Thus, the cooperativeness of transcription factors at the level of hotspots and superenhancers is very important for the activity of enhancers and transcriptional reprogramming, and hotspots and superenhancers are important regulatory centers for integrating the influence of external signals on chromatin.
(Fig. Cell Reports)
Professor Mandrup and her colleagues proved not only the fact of the existence of hot spots, but also that often several such points are close to each other and form large so-called superenhancers. Apparently, such superenhancers are extremely important for the activation of the necessary genes during the differentiation of a stem cell into an adipocyte.
Thus, this study shows an extremely high degree of cooperation between transcription factors at the DNA level, which seems very important for choosing the direction of stem cell differentiation.
While studying the processes of differentiation of adipose tissue stem cells, scientists also pursue medical goals.
"We know that there are two types of fat cells – brown and white. The cells of white adipose tissue accumulate fat, and the cells of brown fat actually enhance its burning. Brown fat cells are found mainly in infants, but they are also present in adults in different quantities. If we can find ways to make stem cells develop into brown rather than white fat cells, we can suppress the development of obesity. Emphasizing the importance of specific DNA sites where proteins interact, the results of our work open up new opportunities in this direction," the researchers say about their work.
Portal "Eternal youth" http://vechnayamolodost.ru26.08.2014