Transcriptomic and Epigenetic Signatures of Mouse Cardiac Progenitor Cells
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ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Yiqiang Zhang
PROVIDER: E-GEOD-49683 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Adult cardioyocytes undergo remarkable dedifferentiation and cell cycle reprogramming/reentery when cultured in mitogen-rich medium, continuously, and give rise to cardiac progenitor cells (CPCs). Using microfluidic device for single-cell capture and whole-transcriptomic amplification, we analyze the whole-genome transcriptomic profile in adult mouse cardiomyocytes (Ctl) and in their derived CPCs, and validate the gene expression by single-cell PCR and PCR array. Using two platforms for DNA methylation profiling: NimbleGen DNA methylation array and CHARM array, the whole-genome DNA methylation profile in myocytes (Ctl) and CPCs were compared and their regulations in relationship to the transcriptomics profile were analyzed. The results demonstrated remarkable molecular reprogramming pertaining to dedifferentiation, loss of cardiac contractile, structure, and fucntion molecules, and reactivation of cell cycle and proliferation genes, significant changes in metabolisms. The reduction of cardiac function and structure genes are highly related to their hypermethylation of the promoter regions. GO and Pathway enrichment analysis revealed distinct coordianted transcriptomic and epigenetic regulation in the CPCs derived from cardiomyocytes. Genomic DNA isolated from adult mouse cardiomyocytes (Ctl) or cardiomyocyte-derived progenitor cells (CPCs) was subjected to digestion by methylcytosine-sensitive enzyme McrBC, and subsequently purification and amplification, labeling and hybridization to the NimbleGen 3x720K DNA methylation Promoter array, according to NimbleGen protocol. Percentage methylation, hypermethylation or hypomethylation, and peak enrichment were assessed using CHARM protocol.
2016-07-24 | E-GEOD-49678 | biostudies-arrayexpress
Project description:Adult cardioyocytes undergo remarkable dedifferentiation and cell cycle reprogramming/reentery when cultured in mitogen-rich medium, continuously, and give rise to cardiac progenitor cells (CPCs). Using microfluidic device for single-cell capture and whole-transcriptomic amplification, we analyze the whole-genome transcriptomic profile in adult mouse cardiomyocytes (Ctl) and in their derived CPCs, and validate the gene expression by single-cell PCR and PCR array. Using two platforms for DNA methylation profiling: NimbleGen DNA methylation array and CHARM array, the whole-genome DNA methylation profile in myocytes (Ctl) and CPCs were compared and their regulations in relationship to the transcriptomics profile were analyzed. The results demonstrated remarkable molecular reprogramming pertaining to dedifferentiation, loss of cardiac contractile, structure, and function molecules, and reactivation of cell cycle and proliferation genes, significant changes in metabolisms. The reduction of cardiac function and structure genes are highly related to their hypermethylation of the promoter regions. GO and Pathway enrichment analysis revealed distinct coordianted transcriptomic and epigenetic regulation in the CPCs derived from cardiomyocytes. Genomic DNA isolated from adult mouse cardiomyocytes (Ctl) or cardiomyocyte-derived progenitor cells (CPCs) was subjected to digestion by methylcytosine-sensitive enzyme McrBC, and subsequently purification and amplification, labeling and hybridization according to NimbleGen protocol. Percentage methylation, hypermethylation or hypomethylation, and peak enrichment were assessed using CHARM protocol.
2016-07-24 | E-GEOD-49676 | biostudies-arrayexpress
Project description:The Eastern woodchuck (Marmota monax) is naturally infected with woodchuck hepatitis virus (WHV), a hepadnavirus closely related to the human hepatitis B virus (HBV). The woodchuck is used as an animal model for studying chronic hepatitis B (CHB) and HBV-associated hepatocellular carcinoma (HCC) in humans, but the lack of sequence information has hitherto precluded functional genomics analysis. To address this major limitation of the model, we report here the sequencing, assembly and annotation of the woodchuck transcriptome, together with the generation of custom woodchuck microarrays. Using this new platform, we characterized the transcriptional response to persistent WHV infection and WHV-induced HCC. This revealed that chronic WHV infection, like HBV, is associated with (i) a limited intrahepatic type I interferon response, (ii) intrahepatic induction of markers associated with T cell exhaustion, (iii) elevated levels of suppressor of cytokine signaling 3 (SOCS3) in the liver, and (iv) intrahepatic accumulation of neutrophils. Underscoring the translational value of the woodchuck model, this study also determined that WHV-induced HCC shares molecular characteristics with a subtype of human HCC with poor prognosis. Conclusion: Our data establish the translational value of the woodchuck model and provide new insights into immune pathways which may play a role either in the persistence of HBV infection or the sequelae of CHB. Custom microarrays, generated from sequences obtained in transcriptome sequencing of woodchuck liver and PBMCs, were used to examine spleen gene expression in animals chronically infected with WHV (n=4), animals that had resolved WHV infection at least 12 months prior (R; n=4; range 12-18 months), and uninfected animals (U; n=2). Multiple technical replicates per woodchuck sample are included.
2012-04-10 | E-GEOD-36544 | biostudies-arrayexpress
Project description:The Eastern woodchuck (Marmota monax) is naturally infected with woodchuck hepatitis virus (WHV), a hepadnavirus closely related to the human hepatitis B virus (HBV). The woodchuck is used as an animal model for studying chronic hepatitis B (CHB) and HBV-associated hepatocellular carcinoma (HCC) in humans, but the lack of sequence information has hitherto precluded functional genomics analysis. To address this major limitation of the model, we report here the sequencing, assembly and annotation of the woodchuck transcriptome, together with the generation of custom woodchuck microarrays. Using this new platform, we characterized the transcriptional response to persistent WHV infection and WHV-induced HCC. This revealed that chronic WHV infection, like HBV, is associated with (i) a limited intrahepatic type I interferon response, (ii) intrahepatic induction of markers associated with T cell exhaustion, (iii) elevated levels of suppressor of cytokine signaling 3 (SOCS3) in the liver, and (iv) intrahepatic accumulation of neutrophils. Underscoring the translational value of the woodchuck model, this study also determined that WHV-induced HCC shares molecular characteristics with a subtype of human HCC with poor prognosis. Conclusion: Our data establish the translational value of the woodchuck model and provide new insights into immune pathways which may play a role either in the persistence of HBV infection or the sequelae of CHB. Custom microarrays, generated from sequences obtained in transcriptome sequencing of woodchuck liver and PBMCs, were used to examine kidney gene expression in animals chronically infected with WHV (n=5), animals that had resolved WHV infection at least 12 months prior (R; n=4; range 12-18 months), and uninfected animals (U; n=3). Multiple technical replicates per woodchuck sample are included.
2012-04-10 | E-GEOD-36541 | biostudies-arrayexpress
Project description:The Eastern woodchuck (Marmota monax) is naturally infected with woodchuck hepatitis virus (WHV), a hepadnavirus closely related to the human hepatitis B virus (HBV). The woodchuck is used as an animal model for studying chronic hepatitis B (CHB) and HBV-associated hepatocellular carcinoma (HCC) in humans, but the lack of sequence information has hitherto precluded functional genomics analysis. To address this major limitation of the model, we report here the sequencing, assembly and annotation of the woodchuck transcriptome, together with the generation of custom woodchuck microarrays. Using this new platform, we characterized the transcriptional response to persistent WHV infection and WHV-induced HCC. This revealed that chronic WHV infection, like HBV, is associated with (i) a limited intrahepatic type I interferon response, (ii) intrahepatic induction of markers associated with T cell exhaustion, (iii) elevated levels of suppressor of cytokine signaling 3 (SOCS3) in the liver, and (iv) intrahepatic accumulation of neutrophils. Underscoring the translational value of the woodchuck model, this study also determined that WHV-induced HCC shares molecular characteristics with a subtype of human HCC with poor prognosis. Conclusion: Our data establish the translational value of the woodchuck model and provide new insights into immune pathways which may play a role either in the persistence of HBV infection or the sequelae of CHB. Custom microarrays, generated from sequences obtained in transcriptome sequencing of woodchuck liver and PBMCs, were used to examine liver gene expression in animals chronically infected with WHV (n=13), animals that had resolved WHV infection at least 12 months prior (R; n=11; range 12-18 months), and uninfected animals (U; n=10). Multiple technical replicates per woodchuck sample are included.
2012-04-10 | E-GEOD-36533 | biostudies-arrayexpress
Project description:The Eastern woodchuck (Marmota monax) is naturally infected with woodchuck hepatitis virus (WHV), a hepadnavirus closely related to the human hepatitis B virus (HBV). The woodchuck is used as an animal model for studying chronic hepatitis B (CHB) and HBV-associated hepatocellular carcinoma (HCC) in humans, but the lack of sequence information has hitherto precluded functional genomics analysis. To address this major limitation of the model, we report here the sequencing, assembly and annotation of the woodchuck transcriptome, together with the generation of custom woodchuck microarrays. Using this new platform, we characterized the transcriptional response to persistent WHV infection and WHV-induced HCC. This revealed that chronic WHV infection, like HBV, is associated with (i) a limited intrahepatic type I interferon response, (ii) intrahepatic induction of markers associated with T cell exhaustion, (iii) elevated levels of suppressor of cytokine signaling 3 (SOCS3) in the liver, and (iv) intrahepatic accumulation of neutrophils. Underscoring the translational value of the woodchuck model, this study also determined that WHV-induced HCC shares molecular characteristics with a subtype of human HCC with poor prognosis. Conclusion: Our data establish the translational value of the woodchuck model and provide new insights into immune pathways which may play a role either in the persistence of HBV infection or the sequelae of CHB. Custom microarrays, generated from sequences obtained in transcriptome sequencing of woodchuck liver and PBMCs, were used to examine non-tumor vs. tumor gene expression in liver samples obtained from animals chronically infected with WHV (n=13). Multiple technical replicates per woodchuck sample are included.
2012-04-10 | E-GEOD-36545 | biostudies-arrayexpress
Project description:The woodchuck model of hepatitis B virus (HBV) infection displays many characteristics of human infection and has particular value for characterizing the host immune responses during the development of chronic infection. Using the newly developed custom woodchuck microarray platform, we compared the intrahepatic transcriptional responses of neonatal woodchucks with self-limiting and progressing persistent infection with woodchuck hepatitis virus (WHV). This revealed that WHV does not induce intrahepatic gene expression during the early acute stage of infection (8 weeks), suggesting it is a M-bM-^@M-^\stealthM-bM-^@M-^] virus. At the mid-acute phase of infection (14 weeks), resolution was associated with induction of a prominent cytotoxic T cell signature, with perforin and other markers of immune-mediated cytotolytic response being strongly expressed. Strikingly, this was accompanied by high level expression of PD-1 and various other inhibitory T cell receptors, which likely act to minimize liver damage by cytotoxic T cells during viral clearance. Conversely, self-limiting infection was not associated with a strong interferon-M-NM-1/M-NM-2 (IFN-M-NM-1/M-NM-2) transcriptional response, while the IFN-M-NM-3 signaling response (as measured by expression of CXCL9) in the mid-acute phase was comparable to that in chronically infected adult animals. Nevertheless, viperin and other antiviral genes were differentially expressed during resolving infection, suggesting that a subset of interferon-stimulated genes (ISGs) may play a role in the control of WHV replication. Conclusion: This study identifies new immune pathways associated with the clearance of hepadnavirus infection and reveals novel targets with potential for the treatment of chronic hepatitis B. Neonatal woodchucks of both genders were infected at 3 days of age with the same WHV7P1 inoculum containing 5 x 106 WID50 of WHV strain WHV7-11. Custom microarrays were generated from sequences obtained in transcriptome sequencing of woodchuck liver and PBMCs, and were used to examine liver gene expression in animals which eventually become chronically infected with WHV (8 weeks, n=5; 14 weeks, n=9), animals that eventually resolve WHV infection (8 weeks, n=10;14 weeks, n=7) and uninfected animals (8 weeks, n=5;14 weeks,n=5).
2012-09-22 | E-GEOD-37683 | biostudies-arrayexpress
Project description:Enhancers can regulate the transcription of genes over long genomic distances. This is thought to lead to selection against genomic rearrangements within such regions that may disrupt this functional linkage. We tested this concept experimentally using the human X chromosome. We describe a scoring method to identify evolutionary maintenance of linkage between conserved non-coding elements and neighbouring genes. Chromatin marks associated with enhancer function are strongly correlated with the linkage score. We tested more than 1,000 putative enhancers by transgenesis assays in zebrafish to ascertain the identity of the target gene, with a focus on genes involved in X-linked intellectual disabilities (ID). The majority of active enhancers drive a transgenic expression in a pattern consistent with the known expression of a linked gene. These results show that evolutionary maintenance of linkage is a reliable predictor of an enhancer's function, and provide new information to discover the genetic basis of diseases caused by the mis-regulation of gene expression. ChIP-chip from human fetal brain using H3K27Ac or H3K4Me1 antibodies. Biological replicates: H3K27Ac_Rep1, H3K27Ac_Rep2 Biological replicates: H3K4Me1_Rep1, H3K4Me1_Rep2
2015-01-30 | E-GEOD-57354 | biostudies-arrayexpress
Project description:Enhancers can regulate the transcription of genes over long genomic distances. This is thought to lead to selection against genomic rearrangements within such regions that may disrupt this functional linkage. We tested this concept experimentally using the human X chromosome. We describe a scoring method to identify evolutionary maintenance of linkage between conserved non-coding elements and neighbouring genes. Chromatin marks associated with enhancer function are strongly correlated with the linkage score. We tested more than 1,000 putative enhancers by transgenesis assays in zebrafish to ascertain the identity of the target gene, with a focus on genes involved in X-linked intellectual disabilities (ID). The majority of active enhancers drive a transgenic expression in a pattern consistent with the known expression of a linked gene. These results show that evolutionary maintenance of linkage is a reliable predictor of an enhancer's function, and provide new information to discover the genetic basis of diseases caused by the mis-regulation of gene expression. ChIP-chip from mouse 14.5 days fetal brain using P300 or H3K4Me1 antibodies. Biological replicates: P300_Rep1, P300_Rep2 Biological replicates: H3K4Me1_Rep1,H3K4Me1_Rep2
2015-01-30 | E-GEOD-57357 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE36533: Transcriptomic analysis of the woodchuck model of chronic hepatitis B: Liver gene expression in uninfected, resolved and chronically infected woodchucks GSE36541: Transcriptomic analysis of the woodchuck model of chronic hepatitis B: Kidney gene expression in uninfected, resolved and chronically infected woodchucks GSE36544: Transcriptomic analysis of the woodchuck model of chronic hepatitis B: Spleen gene expression in uninfected, resolved and chronically infected woodchucks GSE36545: Transcriptomic analysis of the woodchuck model of chronic hepatitis B: Liver gene expression in tumor and non-tumor samples from chronically infected woodchucks Refer to individual Series
2012-04-10 | E-GEOD-36250 | biostudies-arrayexpress