Skolkovo Institute for Science and Technology

Skolkovo, Russia

Skolkovo Institute for Science and Technology

Skolkovo, Russia
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Zhang B.,University of Chinese Academy of Sciences | Han D.,Chinese Academy of Sciences | Korostelev Y.,Moscow State University | Yan Z.,La Trobe University | And 6 more authors.
Genome biology and evolution | Year: 2016

Small nuclear and nucleolar RNAs (snRNAs and snoRNAs) are known to be functionally and evolutionarily conserved elements of transcript processing machinery. Here, we investigated the expression evolution of snRNAs and snoRNAs by measuring their abundance in the frontal cortex of humans, chimpanzees, rhesus monkeys, and mice. Although snRNA expression is largely conserved, 44% of the 185 measured snoRNA and 40% of the 134 snoRNA families showed significant expression divergence among species. The snRNA and snoRNA expression divergence included drastic changes unique to humans: A 10-fold elevated expression ofU1snRNA and a 1,000-fold drop in expression ofSNORA29 The decreased expression ofSNORA29might be due to two mutations that affect secondary structure stability. Using in situ hybridization, we further localizedSNORA29expression to nucleolar regions of neuronal cells. Our study presents the first observation of snoRNA abundance changes specific to the human lineage and suggests a possible mechanism underlying these changes. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Li Q.,Chinese Academy of Sciences | Li Q.,University of Chinese Academy of Sciences | Bozek K.,Okinawa Institute of Science and Technology | Xu C.,Chinese Academy of Sciences | And 14 more authors.
Molecular Biology and Evolution | Year: 2017

Lipids are essential components of the brain. Here, we conducted a comprehensive mass spectrometry-based analysis of lipidome composition in the prefrontal cortex of 40 humans, 40 chimpanzees, and 40 rhesus monkeys over postnatal development and adulthood. Of the 11,772 quantified lipid peaks, 7,589 change significantly along the lifespan. More than 60% of these changes occur prior to adulthood, with less than a quarter associated with myelination progression. Evolutionarily, 36% of the age-dependent lipids exhibit concentration profiles distinct to one of the three species; 488 (18%) of them were unique to humans. In both humans and chimpanzees, the greatest extent of species-specific differences occurs in early development. Human-specific lipidome differences, however, persist over most of the lifespan and reach their peak from 20 to 35 years of age, when compared with chimpanzee-specific ones. © 2017 The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved.

Raven A.,University of Edinburgh | Lu W.-Y.,University of Edinburgh | Man T.Y.,University of Edinburgh | Ferreira-Gonzalez S.,University of Edinburgh | And 10 more authors.
Nature | Year: 2017

After liver injury, regeneration occurs through self-replication of hepatocytes. In severe liver injury, hepatocyte proliferation is impaired - a feature of human chronic liver disease. It is unclear whether other liver cell types can regenerate hepatocytes. Here we use two independent systems to impair hepatocyte proliferation during liver injury to evaluate the contribution of non-hepatocytes to parenchymal regeneration. First, loss of β1-integrin in hepatocytes with liver injury triggered a ductular reaction of cholangiocyte origin, with approximately 25% of hepatocytes being derived from a non-hepatocyte origin. Second, cholangiocytes were lineage traced with concurrent inhibition of hepatocyte proliferation by β1-integrin knockdown or p21 overexpression, resulting in the significant emergence of cholangiocyte-derived hepatocytes. We describe a model of combined liver injury and inhibition of hepatocyte proliferation that causes physiologically significant levels of regeneration of functional hepatocytes from biliary cells. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.

Stefanov Y.P.,RAS Institute of Strength Physics and Materials Science | Myasnikov A.V.,Skolkovo Institute for Science and Technology
AIP Conference Proceedings | Year: 2015

The paper presents numerical modeling results on plastic deformation development around vertical and horizontal wells in rocks for four lithologies typical of the Bazhenov formation. Estimates of irreversible deformation were obtained depending on wellbore pressure, in-situ stress distribution and rock dilation factor. Computational results showed that for the considered lithology borehole pressure management does not always provide wellbore stability if the contrast between principal stresses is large enough. © 2015 AIP Publishing LLC.

de Jong J.,Netherlands Cancer Institute | Akhtar W.,Netherlands Consortium for Systems Biology | Akhtar W.,Netherlands Cancer Institute | Badhai J.,Netherlands Cancer Institute | And 9 more authors.
PLoS Genetics | Year: 2014

The ability of retroviruses and transposons to insert their genetic material into host DNA makes them widely used tools in molecular biology, cancer research and gene therapy. However, these systems have biases that may strongly affect research outcomes. To address this issue, we generated very large datasets consisting of ~120000 to ~180000 unselected integrations in the mouse genome for the Sleeping Beauty (SB) and piggyBac (PB) transposons, and the Mouse Mammary Tumor Virus (MMTV). We analyzed ~80 (epi)genomic features to generate bias maps at both local and genome-wide scales. MMTV showed a remarkably uniform distribution of integrations across the genome. More distinct preferences were observed for the two transposons, with PB showing remarkable resemblance to bias profiles of the Murine Leukemia Virus. Furthermore, we present a model where target site selection is directed at multiple scales. At a large scale, target site selection is similar across systems, and defined by domain-oriented features, namely expression of proximal genes, proximity to CpG islands and to genic features, chromatin compaction and replication timing. Notable differences between the systems are mainly observed at smaller scales, and are directed by a diverse range of features. To study the effect of these biases on integration sites occupied under selective pressure, we turned to insertional mutagenesis (IM) screens. In IM screens, putative cancer genes are identified by finding frequently targeted genomic regions, or Common Integration Sites (CISs). Within three recently completed IM screens, we identified 7%-33% putative false positive CISs, which are likely not the result of the oncogenic selection process. Moreover, results indicate that PB, compared to SB, is more suited to tag oncogenes. © 2014 de Jong et al.

Wei Y.-N.,Chinese Academy of Sciences | Wei Y.-N.,University of Chinese Academy of Sciences | Hu H.-Y.,Chinese Academy of Sciences | Xie G.-C.,Chinese Academy of Sciences | And 7 more authors.
Genome Biology | Year: 2015

Background: In studies of development and aging, the expression of many genes has been shown to undergo drastic changes at mRNA and protein levels. The connection between mRNA and protein expression level changes, as well as the role of posttranscriptional regulation in controlling expression level changes in postnatal development and aging, remains largely unexplored. Results: Here, we survey mRNA and protein expression changes in the prefrontal cortex of humans and rhesus macaques over developmental and aging intervals of both species' lifespans. We find substantial decoupling of mRNA and protein expression levels in aging, but not in development. Genes showing increased mRNA/protein disparity in primate brain aging form expression patterns conserved between humans and macaques and are enriched in specific functions involving mammalian target of rapamycin (mTOR) signaling, mitochondrial function and neurodegeneration. Mechanistically, aging-dependent mRNA/protein expression decoupling could be linked to a specific set of RNA binding proteins and, to a lesser extent, to specific microRNAs. Conclusions: Increased decoupling of mRNA and protein expression profiles observed in human and macaque brain aging results in specific co-expression profiles composed of genes with shared functions and shared regulatory signals linked to specific posttranscriptional regulators. Genes targeted and predicted to be targeted by the aging-dependent posttranscriptional regulation are associated with biological processes known to play important roles in aging and lifespan extension. These results indicate the potential importance of posttranscriptional regulation in modulating aging-dependent changes in humans and other species. © 2015 Wei et al.

Liu X.,Chinese Academy of Sciences | Liu X.,Jinan University | Liu X.,Institute of Forensic science | Han D.,Chinese Academy of Sciences | And 17 more authors.
PLoS Biology | Year: 2016

Cognitive defects in autism spectrum disorder (ASD) include socialization and communication: key behavioral capacities that separate humans from other species. Here, we analyze gene expression in the prefrontal cortex of 63 autism patients and control individuals, as well as 62 chimpanzees and macaques, from natal to adult age. We show that among all aberrant expression changes seen in ASD brains, a single aberrant expression pattern overrepresented in genes involved synaptic-related pathways is enriched in nucleotide variants linked to autism. Furthermore, only this pattern contains an excess of developmental expression features unique to humans, thus resulting in the disruption of human-specific developmental programs in autism. Several members of the early growth response (EGR) transcription factor family can be implicated in regulation of this aberrant developmental change. Our study draws a connection between the genetic risk architecture of autism and molecular features of cortical development unique to humans. © 2016 Public Library of Science. All rights reserved.

Bozek K.,Chinese Academy of Sciences | Bozek K.,Max Planck Institute for Evolutionary Anthropology | Wei Y.,Chinese Academy of Sciences | Yan Z.,Chinese Academy of Sciences | And 15 more authors.
Neuron | Year: 2015

Lipids are prominent components of the nervous system. Here we performed a large-scale mass spectrometry-based analysis of the lipid composition of three brain regions as well as kidney and skeletal muscle of humans, chimpanzees, rhesus macaques, and mice. The human brain shows the most distinct lipid composition: 76% of 5,713 lipid compounds examined in our study are either enriched or depleted in the human brain. Concentration levels of lipids enriched in the brain evolve approximately four times faster among primates compared with lipids characteristic of non-neural tissues and show further acceleration of change in human neocortical regions but not in the cerebellum. Human-specific concentration changes are supported by human-specific expression changes for corresponding enzymes. These results provide the first insights into the role of lipids in human brain evolution. © 2015 Elsevier Inc.

Akhtar W.,Netherlands Cancer Institute | Pindyurin A.V.,Netherlands Cancer Institute | Pindyurin A.V.,Russian Academy of Sciences | De Jong J.,Netherlands Cancer Institute | And 9 more authors.
Nature Protocols | Year: 2014

The influence of local chromatin context on gene expression can be explored by integrating a transcription reporter at different locations in the genome as a sensor. Here we provide a detailed protocol for analyzing thousands of reporters integrated in parallel (TRIP) at a genome-wide level. TRIP is based on tagging each reporter with a unique barcode, which is used for independent reporter expression analysis and integration site mapping. Compared with previous methods for studying position effects, TRIP offers a 100-1,000-fold higher throughput in a faster and less-labor-intensive manner. The entire experimental protocol takes â ̂1/442 d to complete, with high-throughput sequencing and data analysis requiring an additional â ̂1/411 d. TRIP was developed by using transcription reporters in mouse embryonic stem (mES) cells, but because of its flexibility the method can be used to probe the influence of chromatin context on a variety of molecular processes in any transfectable cell line. © 2014 Nature America, Inc.

PubMed | Skolkovo Institute for Science and Technology and Moscow State University
Type: Journal Article | Journal: Journal of molecular biology | Year: 2016

N6-methyladenosine (m(6)A) is ubiquitously present in the RNA of living organisms from Escherichia coli to humans. Methyltransferases that catalyze adenosine methylation are drastically different in specificity from modification of single residues in bacterial ribosomal or transfer RNA to modification of thousands of residues spread among eukaryotic mRNA. Interactions that are formed by m(6)A residues range from RNA-RNA tertiary contacts to RNA-protein recognition. Consequences of the modification loss might vary from nearly negligible to complete reprogramming of regulatory pathways and lethality. In this review, we summarized current knowledge on enzymes that introduce m(6)A modification, ways to detect m(6)A presence in RNA and the functional role of this modification everywhere it is present, from bacteria to humans.

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