10 March 2010

Last week at Nature publishing group

The most interesting publications are in the latest issues of journals included in the Nature publishing group, according to Genomeweb site reviewers.

Microbiome metagenomeScientists have created a catalog of the genes of the human microbiome – the types of microbes that inhabit the human intestine.

According to recent estimates (and to the horror of some authors of newspaper articles and their readers :), up to 100 trillion bacterial cells coexist in our organisms, which is an order of magnitude greater than the total number of cells in the human body, and microbial genomes, collectively, encode 100 times more genes than the human genome. The main part of the microbial mass lives in our intestines and participates in the processes of assimilation of nutrients by the human body. Human health largely depends on the state of the intestinal microflora, and a change in its composition can provoke the occurrence of inflammatory bowel diseases and obesity. Studies have shown that the composition of the intestinal microflora can vary significantly in healthy people, although these differences are more pronounced in children than in adults. The study of the composition and functioning of the intestinal microflora will allow us to more accurately establish the relationship between its condition and specific human diseases.

In the article A human gut microbial gene catalog established by metagenomic sequencing, published in the latest issue of the journal Nature, an international team of scientists presented the results of sequencing 576.7 billion pairs of DNA nucleotides isolated from stool samples of 124 residents of Denmark and Spain, and analysis of 3.3 million microbial genes included in the sequenced sequences. It turned out that 99% of the sequenced genes belong to 1000-1150 species of bacteria, of which at least 160 of the most common species are found in the intestines of each of the examined. The catalog of intestinal microflora compiled by the researchers will further determine the functions necessary for the existence of bacteria in the intestine.

Vascular endothelium from embryonic stem cells: fluorescence will confirm the increase in the performance of the methodIn the field of differentiation of human embryonic stem cells (ESCs) into endothelial cells, there was a problem of obtaining a steadily growing population of blood vessel cells.

The method of long-term cultivation of endothelial cells derived from ESCs, developed by a group of New York scientists, is described in the article Expansion and maintenance of human embryonic stem cell–derived endothelial cells by TGFß inhibition is Id1 dependent, published in the latest issue of the journal Nature Biotechnology. Caused by inhibition of transforming growth factor beta (TGF-beta), the production of Id1 protein (inhibitor of differentiation - inhibitor of cell differentiation) in endothelial cells derived from human ESCs is necessary for enhanced proliferation and preservation of the differentiated state of these cells. To determine the ways of differentiation of ESCs into vascular cells, as well as to enhance cell division, the researchers screened the factors determining the development of ESCs into endothelial cells using the hVPr-GFP reporter construct. In such a gene bundle, the green fluorescent protein (GFP) is controlled by the promoter of the VE-cadherin gene, encoding a transmembrane protein specific to endothelial cells. As a result, factors activating the production of proteins specific to endothelial cells in cells simultaneously activate the promoter of the VE-cadherin gene, thereby increasing the synthesis of GFP. According to the method proposed by scientists, inhibition of TGF-beta on day 7 from the start of differentiation led to a tenfold increase in cells containing GFP (hVPr-GFP), and repeated inhibition caused a 36-fold increase in the number of endothelial cells that formed homogeneous monolayers in culture and expressed proteins characteristic of endothelial cells. Using a similar hVPr-GFP construct Id1-YFP containing yellow Fluorescent Protein (YFP), scientists have found the dependence of increased Id1 protein production and enhanced proliferation of endothelial cells transformed from ESC on TGF-beta inhibition. The method developed by scientists allows to obtain stably proliferating endothelial cells from ESCs at a level suitable for clinical use.

Celiac disease and snips: Unlucky number 13In the article Multiple common variants for celiac disease influencing immune gene expression, published in the journal Nature Genetics, an international group of scientists managed to identify multiple common variants of gene polymorphism affecting the expression of immune system genes in celiac disease – a hereditary autoimmune disease manifested in digestive disorders caused by damage to the villi of the small intestine by products containing gluten (rye, wheat, oats, malt).

Using the method of large-scale associative study of the genome (Genome–Wide Association Study, GWAS) of the second generation, which allows to establish a statistically reliable relationship between the observed characteristics of the organism (for example, a specific hereditary disease) and a characteristic genotype or genetic marker, which is often represented by snips - DNA sequences differing by one nucleotide (single-nucleotide polymorphism, SNP), the researchers analyzed specific snips of 4,533 patients with celiac disease and 10,750 people who do not suffer from this disease and make up the control group. Among the studied SNPs, scientists found 13 regions of the genome associated with celiac disease, most of which turned out to be associated with the genes of the immune system.

Daria Chervyakova
Portal "Eternal youth" http://vechnayamolodost.ru based on Genomeweb materials: This Week in Nature, March 04, 2010

10.03.2010

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