Homo sapiens
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PROVIDER: PRJNA112707 | ENA |
REPOSITORIES: ENA
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Project description:Apoptosis plays a pivotal role in embryogenesis and postnatal cell homeostasis, involving DNA or subcellular fragmentation, and shedding of small membranous microvesicles termed apoptotic bodies (AB). Following DNA damage, hypoxia, or vascular injury, the chemokine CXCL12 has been implicated in the recruitment of progenitor cells for tissue regeneration through its receptor CXCR4 and in mechanisms counteracting apoptosis. Whether AB deliver alarm signals for regenerative responses to neighbouring cells beyond recruitment or eat-me signals for phagocytes and relevance to diseases with abundant apoptosis, eg atherosclerosis, remains unknown. Here we show that endothelial cell-derived AB are generated during diet-induced atherosclerosis and can be transferred to recipient endothelial or smooth muscle cells to induce functional expression of CXCL12. This is mediated through miRNA-126 enriched in AB, which acts by silencing RGS16 translation and unlocking CXCR4 to unleash an auto-regulatory feedback loop inducing CXCL12. Injection of AB promoted mobilization and incorporation of progenitor cells, reducing diet-induced atherosclerosis in apolipoprotein E-deficient mice, and local transfer of microRNA-126 inhibited collar-induced arterial plaque formation. This was associated with increased smooth muscle content but decreased macrophage and apoptotic cell content, all features of plaque stability. Our data identify a new mechanism, by which AB confer microRNA-126 as a paracrine alarm messenger to enhance CXCR4 signals and CXCL12 expression, thereby limiting or repairing vascular damage. This adds to the important functions of microRNAs in health and disease and may extend to progenitor cell recruitment during other forms of tissue repair or homeostasis. AB were isolated from supernatants of apoptotic, serum-starved human umbilical vein endothelial cells (HUVECs) by sequential centrifugation steps. Total RNA was isolated from AB or HUVECs and microRNA was purified using the mirVanaTM miRNA Isolation Kit (Ambion). microRNA obtained from 10 µg of total RNA was labeled using the mirVanaTM miRNA Labeling Kit (Ambion) and fluorescent Cy3 (Molecular Probes), and hybridized to the Ambion mirVanaTM miRNA Bioarray (1566 v.1). Hybridized mirVana miRNA Bioarrays were scanned and quantified by using ImaGene 5.5.4 (Bio Discovery). Resulted signal intensities were background corrected and then normalized using variance stabilization normalization. (Huber, 2002).
2010-08-31 | E-GEOD-12696 | biostudies-arrayexpress
Project description:Apoptosis plays a pivotal role in embryogenesis and postnatal cell homeostasis, involving DNA or subcellular fragmentation, and shedding of small membranous microvesicles termed apoptotic bodies (AB). Following DNA damage, hypoxia, or vascular injury, the chemokine CXCL12 has been implicated in the recruitment of progenitor cells for tissue regeneration through its receptor CXCR4 and in mechanisms counteracting apoptosis. Whether AB deliver alarm signals for regenerative responses to neighbouring cells beyond recruitment or eat-me signals for phagocytes and relevance to diseases with abundant apoptosis, eg atherosclerosis, remains unknown. Here we show that endothelial cell-derived AB are generated during diet-induced atherosclerosis and can be transferred to recipient endothelial or smooth muscle cells to induce functional expression of CXCL12. This is mediated through miRNA-126 enriched in AB, which acts by silencing RGS16 translation and unlocking CXCR4 to unleash an auto-regulatory feedback loop inducing CXCL12. Injection of AB promoted mobilization and incorporation of progenitor cells, reducing diet-induced atherosclerosis in apolipoprotein E-deficient mice, and local transfer of microRNA-126 inhibited collar-induced arterial plaque formation. This was associated with increased smooth muscle content but decreased macrophage and apoptotic cell content, all features of plaque stability. Our data identify a new mechanism, by which AB confer microRNA-126 as a paracrine alarm messenger to enhance CXCR4 signals and CXCL12 expression, thereby limiting or repairing vascular damage. This adds to the important functions of microRNAs in health and disease and may extend to progenitor cell recruitment during other forms of tissue repair or homeostasis.
2010-08-31 | GSE12696 | GEO
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
2010-09-25 | GSE24338 | GEO
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature
Project description:We have sequenced miRNA libraries from human embryonic, neural and foetal mesenchymal stem cells. We report that the majority of miRNA genes encode mature isomers that vary in size by one or more bases at the 3’ and/or 5’ end of the miRNA. Northern blotting for individual miRNAs showed that the proportions of isomiRs expressed by a single miRNA gene often differ between cell and tissue types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins in vivo and were active in luciferase assays, indicating that they are functional. Bioinformatics analysis predicts substantial differences in targeting between miRNAs with minor 5’ differences and in support of this we report that a 5’ isomiR-9-1 gained the ability to inhibit the expression of DNMT3B and NCAM2 but lost the ability to inhibit CDH1 in vitro. This result was confirmed by the use of isomiR-specific sponges. Our analysis of the miRGator database indicates that a small percentage of human miRNA genes express isomiRs as the dominant transcript in certain cell types and analysis of miRBase shows that 5’ isomiRs have replaced canonical miRNAs many times during evolution. This strongly indicates that isomiRs are of functional importance and have contributed to the evolution of miRNA genes
2014-08-06 | GSE58734 | GEO
Project description:As the evolution of miRNA genes has been found to be one of the important factors in formation of the modern type of man, we performed a comparative analysis of the evolution of miRNA genes in two archaic hominines, Homo sapiens neanderthalensis and Homo sapiens denisova, and elucidated the expression of their target mRNAs in bain.A comparative analysis of the genomes of primates, including species in the genus Homo, identified a group of miRNA genes having fixed substitutions with important implications for the evolution of Homo sapiens neanderthalensis and Homo sapiens denisova. The mRNAs targeted by miRNAs with mutations specific for Homo sapiens denisova exhibited enhanced expression during postnatal brain development in modern humans. By contrast, the expression of mRNAs targeted by miRNAs bearing variations specific for Homo sapiens neanderthalensis was shown to be enhanced in prenatal brain development.Our results highlight the importance of changes in miRNA gene sequences in the course of Homo sapiens denisova and Homo sapiens neanderthalensis evolution. The genetic alterations of miRNAs regulating the spatiotemporal expression of multiple genes in the prenatal and postnatal brain may contribute to the progressive evolution of brain function, which is consistent with the observations of fine technical and typological properties of tools and decorative items reported from archaeological Denisovan sites. The data also suggest that differential spatial-temporal regulation of gene products promoted by the subspecies-specific mutations in the miRNA genes might have occurred in the brains of Homo sapiens denisova and Homo sapiens neanderthalensis, potentially contributing to the cultural differences between these two archaic hominines.
| S-EPMC4686780 | biostudies-literature
Project description:PurposeWe investigated the evidence of recent positive selection in the human phototransduction system at single nucleotide polymorphism (SNP) and gene level.MethodsSNP genotyping data from the International HapMap Project for European, Eastern Asian, and African populations was used to discover differences in haplotype length and allele frequency between these populations. Numeric selection metrics were computed for each SNP and aggregated into gene-level metrics to measure evidence of recent positive selection. The level of recent positive selection in phototransduction genes was evaluated and compared to a set of genes shown previously to be under recent selection, and a set of highly conserved genes as positive and negative controls, respectively.ResultsSix of 20 phototransduction genes evaluated had gene-level selection metrics above the 90th percentile: RGS9, GNB1, RHO, PDE6G, GNAT1, and SLC24A1. The selection signal across these genes was found to be of similar magnitude to the positive control genes and much greater than the negative control genes.ConclusionsThere is evidence for selective pressure in the genes involved in retinal phototransduction, and traces of this selective pressure can be demonstrated using SNP-level and gene-level metrics of allelic variation. We hypothesize that the selective pressure on these genes was related to their role in low light vision and retinal adaptation to ambient light changes. Uncovering the underlying genetics of evolutionary adaptations in phototransduction not only allows greater understanding of vision and visual diseases, but also the development of patient-specific diagnostic and intervention strategies.
| S-EPMC3743458 | biostudies-literature
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
2011-02-19 | GSE20463 | GEO
Project description:Cortical thickness has been investigated since the beginning of the 20th century, but we do not know how similar the cortical thickness profiles among humans are. In this study, the local similarity of cortical thickness profiles was investigated using sliding window methods. Here, we show that approximately 5% of the cortical thickness profiles are similarly expressed among humans while 45% of the cortical thickness profiles show a high level of heterogeneity. Therefore, heterogeneity is the rule, not the exception. Cortical thickness profiles of somatosensory homunculi and the anterior insula are consistent among humans, while the cortical thickness profiles of the motor homunculus are more variable. Cortical thickness profiles of homunculi that code for muscle position and skin stimulation are highly similar among humans despite large differences in sex, education, and age. This finding suggests that the structure of these cortices remains well preserved over a lifetime. Our observations possibly relativize opinions on cortical plasticity.
| S-EPMC5738339 | biostudies-literature