Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA152963 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The liver’s remarkable capacity to regenerate allows it to carry out vital life-supporting functions despite unrelenting pathogen and toxin-induced injury. Unchecked, this capability also leads to cirrhosis, a burgeoning global disease burden. Existing animal models only partially recapitulate human liver regeneration, which hitherto has not been systematically studied. We investigated human liver regeneration in a unique model of liver transplantation. Here we show coordinated changes in expression of microRNA (miRNA) during regeneration that drive proliferation, innate immunity and angiogenesis. Failed regeneration is associated with distinct miRNAs enforcing cell cycle inhibition and DNA methylation. The miRNA expression associated with successful or failed regeneration when recapitulated in vitro, triggered expression of cardinal regeneration-linked genes promoting cell cycle entry or inhibition, respectively. Furthermore, inhibition of three miRNAs whose downregulation is associated with successful regeneration, induced proliferation in vitro. Our data indicate that human liver regeneration is orchestrated by distinct miRNAs determining cell cycle fate. Their manipulation may obviate the need for transplantation by enforcing successful regeneration in the liver and other solid organs.
2013-05-06 | GSE36146 | GEO
Project description:The liverM-bM-^@M-^Ys remarkable capacity to regenerate allows it to carry out vital life-supporting functions despite unrelenting pathogen and toxin-induced injury. Unchecked, this capability also leads to cirrhosis, a burgeoning global disease burden. Existing animal models only partially recapitulate human liver regeneration, which hitherto has not been systematically studied. We investigated human liver regeneration in a unique model of liver transplantation. Here we show coordinated changes in expression of microRNA (miRNA) during regeneration that drive proliferation, innate immunity and angiogenesis. Failed regeneration is associated with distinct miRNAs enforcing cell cycle inhibition and DNA methylation. The miRNA expression associated with successful or failed regeneration when recapitulated in vitro, triggered expression of cardinal regeneration-linked genes promoting cell cycle entry or inhibition, respectively. Furthermore, inhibition of three miRNAs whose downregulation is associated with successful regeneration, induced proliferation in vitro. Our data indicate that human liver regeneration is orchestrated by distinct miRNAs determining cell cycle fate. Their manipulation may obviate the need for transplantation by enforcing successful regeneration in the liver and other solid organs. We compared a group of seven patients with successful regeneration (RG) after auxiliary liver transplant (ALT) to four patients who also had ALT but failed to regenerate (NRG). Regeneration was quantified by volume expansion using radiographic imaging; functional recovery was assessed using nuclear isotope scanning and hepatocellular regeneration using histology. Based on histological assessment, three time points were selected for both groups (RG and NRG). Biopsies were taken at the time of transplant and at different intervals post-transplant. Since sample acquisition was driven by clinical necessity, widely discrepant time intervals existed between T=1, T=2 and T=3 for the patients. RNA was extracted from archived histology samples of the RG and NRG, and miRNA expression was analysed using the Affymetrix GeneChip miRNA 1.0 assays. This submission does not include NRG samples taken at time point 3.
2013-05-06 | E-GEOD-36146 | biostudies-arrayexpress
Project description:This study aimed to improve our understanding of the mechanisms of liver regeneration in sharks and to identify the microRNAs that participate in liver regeneration and other liver-related diseases. To this end, normal and regenerating liver tissues from C. plagiosum were harvested 0, 3, 6, 12 and 24 h after partial hepatectomy (PH) and were sequenced using the Illumina/Solexa platform. In total, 309 known microRNAs and 590 novel microRNAs were identified in C. plagiosum. There were 368 microRNAs differentially expressed between the normal and regenerating livers. Using target prediction and GO analysis, most of the differentially expressed microRNAs were assigned to functional categories that may be involved in regulating liver regeneration, such as cell proliferation, differentiation and apoptosis. Additionally, this study adds several novel microRNAs to the database, which will help identify microRNAs in other genetically related species and provides a starting point for future studies aimed at understanding the roles of microRNAs in liver regeneration and other liver diseases.
2016-08-30 | GSE72339 | GEO
Project description:Over 40 % of microRNAs are located in introns of coding genes, and many intronic microRNAs are co-regulated with their host genes. In such cases of co-regulation, the products of host genes and their intronic microRNAs can cooperate to coordinately regulate biologically important pathways. Therefore, we screened intronic microRNAs dysregulated in liver of obese mouse models to identify previously uncharacterized coding host genes that may contribute to the pathogenesis of obesity-associated insulin resistance and type 2 diabetes mellitus. Our approach identified that expression of both Ectodysplasin A (Eda), the causal gene of X-linked hypohidrotic ectodermal dysplasia (XLHED; MIM 305100) and its intronic microRNA, miR-676, was strongly increased in liver of obese mouse models. Moreover, hepatic EDA expression is increased in obese human subjects, reduced upon weight loss, and its hepatic expression correlates with systemic insulin resistance. Eda expression in murine liver is controlled via PPARg activation, increases in circulation and promotes JNK activation and inhibitory serine phosphorylation of IRS1 in skeletal muscle. Consistently, bi-directional modulation of hepatic Eda expression in mouse models affects systemic glucose metabolism with alterations of muscle insulin signaling, revealing a novel role of EDA as an obesity-associated hepatokine, which impairs insulin sensitivity in skeletal muscle.
2017-11-14 | PXD006573 | Pride
Project description:Successful regeneration of injured neurons requires a complex molecular response that involves the expression, modification and transport of large numbers of proteins. The neuronal proteins responsible for the initiation of regenerative neurite outgrowth are largely unknown. Dorsal root ganglion (DRG) neurons display robust and successful regeneration following lesion of their peripheral neurite, whereas outgrowth of central neurites is weak and does not lead to functional recovery. We have utilized this differential response to gain insight in the early transcriptional events associated with successful regeneration. Surprisingly, our study shows that peripheral and central nerve crushes elicit very distinct transcriptional activation, revealing a large set of novel genes that are differentially regulated within the first 24 hours after the lesion. A large number of known regeneration associated genes were retrieved in our study, and, in addition, hundreds of novel genes possibly involved in the transcriptional regulatory network underlying successful regeneration. Please refer to Stam et al., Eur. J. Neurosci 25:3629 (2007). Keywords: time course
2007-07-09 | GSE5762 | GEO
Project description:Previous studies of zebrafish caudal fin regeneration have shown that multiple genetic programs are moduled through regulatory factors. MicroRNAs are short highly conserved non-coding genes that suppress expression of target genes and thereby control multiple genetic programs. Given their important regulatory roles and evolutionary conservation, we hypothesize that microRNAs define a conserved genetic regulatory circuit important for appendage regeneration. We characterized microRNA expression during zebrafish caudal fin regeneration using small RNA sequencing. The stages of caudal fin regeneration were assayed for mRNA expression using mRNA sequencing. Small RNA and mRNA gene expression profiling during 0 and 4 days post amputation.
2016-06-01 | E-GEOD-74415 | biostudies-arrayexpress
Project description:The transcriptome of ejaculates used for successful/failed in vitro-fertilization
| PRJNA140409 | ENA
Project description:The liver has a remarkable ability to regenerate, with the best experimental model for regeneration being partial hepatectomy (PHx), in which up to two-thirds of the liver may be removed, and the residual lobes enlarge to make up for the missing mass in a few days’ time. Liver regeneration has been extensively studied, mainly in rodent models, and characterized in terms of transcriptional regulation of gene expression. However, little is known regarding regulation of gene expression in a human model of regeneration following PHx. We used microarrays to follow gene expression changes shortly following PHx. Experiment Overall Design: Liver tissues were collected from patients undergoing a PHx surgery (1.5, 42 and 81 years) under an IRB approval, at the onset (T0) and shortly after PHx (0.5hr, 1hr and 1.5hrs) for RNA extraction and hybridization on Affymetrix microarrays.
2009-10-10 | E-GEOD-15239 | biostudies-arrayexpress
Project description:Previous studies of appendage regeneration in the axolotl have shown that multiple genetic programs are modulated through regulatory factors. MicroRNAs are short highly conserved non-coding genes that suppress expression of target genes and thereby control multiple genetic programs. Given their important regulatory roles and evolutionary conservation, we hypothesize that microRNAs define a conserved genetic regulatory circuit important for appendage regeneration. We characterized microRNA expression during Axolotl forelimb regeneration using small RNA sequencing. The same samples were assayed for mRNA expression using mRNA sequencing. Small RNA and mRNA gene expression profiling during 0, 3, 6 and 14 days post amputation.
2016-06-01 | E-GEOD-74372 | biostudies-arrayexpress
Project description:Previous studies of vertebrate appendage regeneration have shown that multiple genetic programs are moduled through regulatory factors. MicroRNAs are short highly conserved non-coding genes that suppress expression of target genes and thereby control multiple genetic programs. Given their important regulatory roles and evolutionary conservation, we hypothesize that microRNAs define a conserved genetic regulatory circuit important for appendage regeneration. We characterized microRNA expression during Polypterus senegalus (bichir) pectoral fin regeneration using small RNA sequencing. The same samples were assayed for mRNA expression using mRNA sequencing. Small RNA and mRNA gene expression profiling during 0, 3, 7 and 14 days post amputation.
2016-06-01 | E-GEOD-74374 | biostudies-arrayexpress