Glucocorticoids in maintaining cardiac homeostasis in C57bl/6 (wild-type) mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE83202 | GEO | 2016/06/09
SECONDARY ACCESSION(S): PRJNA325274
REPOSITORIES: GEO
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Project description:To further understand the genomic effects of glucocorticoids in the heart we performed microarray studies on hearts collected from long-term ADX-mice. Our objective is to find cardiac specific genes regulated by glucocorticoids. C57bl/6 (wild-type) mice were adrenalectomized. Hearts were collected from sham-adrenalectomized and adrenalectomized mice 6 months following the surgery. Three biological replicates were used for this study.
2016-06-09 | E-GEOD-83202 | biostudies-arrayexpress
Project description:Adult-onset diseases can be associated with in utero events, but mechanisms for such temporally distant dysregulation of organ function remain unknown. The polycomb histone methyltransferase, Ezh2, stabilizes transcription by depositing repressive histone marks during development that persist into adulthood, but the function of Ezh2-mediated transcriptional stability in postnatal organ homeostasis is not understood. Here, we show that Ezh2 stabilizes the postnatal cardiac gene expression program and prevents cardiac pathology, primarily by repressing the homeodomain transcription factor Six1 in differentiating cardiac progenitors. Loss of Ezh2 in embryonic cardiac progenitors, but not in differentiated cardiomyocytes, resulted in postnatal cardiac pathology, including cardiomyocyte hypertrophy and fibrosis. Loss of Ezh2 caused broad derepression of skeletal muscle genes, including the homeodomain transcription factor Six1, which is expressed in cardiac progenitors but is normally silenced upon cardiac differentiation. Many of the deregulated genes are direct Six1 targets, implying a critical requirement for stable repression of Six1 in cardiac myocytes. Indeed, upon de-repression, Six1 promotes cardiac pathology, as it was sufficient to induce cardiac hypertrophy. Furthermore, genetic reduction of Six1 levels almost completely rescued the pathology of Ezh2-deficient hearts. Thus, repression of a single transcription factor in cardiac progenitors by Ezh2 is essential for stability of the adult heart gene expression program and homeostasis. Our results suggest that epigenetic dysregulation during discrete developmental windows can predispose to adult disease and dysregulated stress responses. Global gene expression profiles of Ezh2-deficient hearts. The right ventricle and the interventricular septum of five wild type (Ezh2f/f) and four Ezh2-deficient (Ezh2f/f;Mef2cAHF::Cre) mice were analyzed.
2011-12-31 | E-GEOD-30076 | biostudies-arrayexpress
Project description:Genome-wide expression analysis of two circadian oscillatory mechanisms in the mouse liver; To identify the genes of which the circadian expression is regulated by endogenous glucocorticoids, we performed DNA microarray analysis using hepatic RNA from adrenalectomized (ADX) and sham-operated mice. Mice were housed in a 12:12 h light-dark cycle (LD12:12; lights on at zeitgeber time (ZT) 0) for at least two weeks before the day of the experiment. Liver samples were dissected, quickly frozen, and stored in liquid nitrogen. Total RNA was purified from pools of 3 animal tissues collected at each time-point using ISOGEN (Nippon Gene Co., Ltd., Japan). Hybridization to Affymetrix GeneChip (MG-U74Av2) arrays proceeded as described (Oishi K et al., J Biol Chem, 278, 41519-41527, 2003). The average difference (AD) value for each gene was provided by GeneChip software. To identify putative glucocorticoid-regulated circadian genes, we compared AD values between two time points (ZT2 and ZT14) in sham operated and in ADX mice. We applied three criteria to the selection of putative glucocorticoid-regulated circadian genes: (i) the AD value is marked as âpresentâ by the GeneChip software in at least one of two time points, (ii) the AD value exhibits a 2-fold or greater change in sham-operated mice and (iii) the fold change is below 2-fold in ADX mice. We identified 169 genes that fluctuated between day and night in the livers of sham-operated mice. Among these, 100 lost circadian rhythmicity in ADX mice. On the other hand, the circadian expression of clock or clock-related genes such as mPer2 and DBP remained almost totally intact in the liver of ADX mice. The present study showed that the circadian expression of one type of liver genes in the mouse is governed by core components of the circadian clock such as CLOCK and BMAL1, and the other depends on endogenous glucocorticoids.
2008-06-12 | E-GEOD-2162 | biostudies-arrayexpress
Project description:Peripheral clocks function to regulate each organ and are synchronized though various molecular and behavioral signals. However, signals that entrain the bladder clock remain elusive. Here, we show that glucocorticoids are a key cue for the bladder clock in vitro and in vivo. A pBmal1-dLuc human urothelial cell line showed significant shifts in gene expression after cortisol treatment while, in vivo, rhythmic bladder clock gene expression was not influenced by bilateral-adrenalectomy (ADx) but shifted 4 hours forward by corticosterone administration at the inactive phase (CORT). Moreover, the bladder clock shifted 8-12 hours in ADx+CORT mice. These mice saw decreases in the diurnal rhythm of volume voided per micturition, while maintaining diurnal activity rhythm. These results indicate that the diurnal rhythm of glucocorticoid signaling is a zeitgeber that overcomes other entrainment factors for the bladder clock and coordinates the diurnal rhythm of volume voided per micturition. (145 words)
2022-06-16 | GSE205971 | GEO
Project description:C57BL6/J mice were treated with anti-PD-1 for 2 or 4 weeks, or with isotype control antibody. In echocardiography, cardiac dysfunction was seen both after 2 and 4 weeks, with decreased ejection fraction and left ventricular dilation. Bulk RNA sequencing of the hearts after treatment was performed to identify the mechanisms of anti-PD-1-induced cardiac dysfunction.
2022-12-03 | E-MTAB-12388 | biostudies-arrayexpress
Project description:Rationale: Neonatal mice have the capacity to regenerate their hearts in response to injury, but this potential is lost after the first week of life. The transcriptional changes that underpin mammalian cardiac regeneration have not been fully characterized at the molecular level. Objective: The objectives of our study were to determine if myocytes revert the transcriptional phenotype to a less differentiated state during regeneration and to systematically interrogate the transcriptional data to identify and validate potential regulators of this process. Methods and Results: We derived a core transcriptional signature of injury-induced cardiac myocyte regeneration in mouse by comparing global transcriptional programs in a dynamic model of in vitro and in vivo cardiac myocyte differentiation, in vitro cardiac myocyte explant model, as well as a neonatal heart resection model. The regenerating mouse heart revealed a transcriptional reversion of cardiac myocyte differentiation processes including reactivation of latent developmental programs similar to those observed during de-stabilization of a mature cardiac myocyte phenotype in the explant model. We identified potential upstream regulators of the core network, including interleukin 13 (IL13), which induced cardiac myocyte cell cycle entry and STAT6/STAT3 signaling in vitro. We demonstrate that STAT3/periostin and STAT6 signaling are critical mediators of IL13 signaling in cardiac myocytes. These downstream signaling molecules are also modulated in the regenerating mouse heart. Conclusions: Our work reveals new insights into the transcriptional regulation of mammalian cardiac regeneration and provides the founding circuitry for identifying potential regulators for stimulating heart regeneration. Comparison of transcriptional programs of primary myocardial tissues sampled from neonatal mice and murine hearts undergoing post-injury regeneration, along with in vitro ESC-differentiated cardiomyocytes
2014-12-20 | E-GEOD-64403 | biostudies-arrayexpress
Project description:Here we define key single-cell transcriptional alterations within cardiac non-myocytes, from ventricles of spontaneously type-2 diabetic (db/db) and control (db/h) mouse hearts ([B6.BKS(D)-Lepr<db>/J], stock #000697). The cell preparation sequenced consisted of metabolically active, live and nucleated non-myocyte cells, which were depleted of endothelial cells. The objective of this experiment was to develop a framework for understanding the dynamics of cardiac cell networks in murine type-2 diabetes, as a resource for future mechanistic studies.
2022-11-29 | E-MTAB-11940 | biostudies-arrayexpress
Project description:Adult-onset diseases can be associated with in utero events, but mechanisms for such temporally distant dysregulation of organ function remain unknown. The polycomb histone methyltransferase, Ezh2, stabilizes transcription by depositing repressive histone marks during development that persist into adulthood, but the function of Ezh2-mediated transcriptional stability in postnatal organ homeostasis is not understood. Here, we show that Ezh2 stabilizes the postnatal cardiac gene expression program and prevents cardiac pathology, primarily by repressing the homeodomain transcription factor Six1 in differentiating cardiac progenitors. Loss of Ezh2 in embryonic cardiac progenitors, but not in differentiated cardiomyocytes, resulted in postnatal cardiac pathology, including cardiomyocyte hypertrophy and fibrosis. Loss of Ezh2 caused broad derepression of skeletal muscle genes, including the homeodomain transcription factor Six1, which is expressed in cardiac progenitors but is normally silenced upon cardiac differentiation. Many of the deregulated genes are direct Six1 targets, implying a critical requirement for stable repression of Six1 in cardiac myocytes. Indeed, upon de-repression, Six1 promotes cardiac pathology, as it was sufficient to induce cardiac hypertrophy. Furthermore, genetic reduction of Six1 levels almost completely rescued the pathology of Ezh2-deficient hearts. Thus, repression of a single transcription factor in cardiac progenitors by Ezh2 is essential for stability of the adult heart gene expression program and homeostasis. Our results suggest that epigenetic dysregulation during discrete developmental windows can predispose to adult disease and dysregulated stress responses.
2011-12-31 | GSE30076 | GEO
Project description:Med13 cardiac over-expression regulates cardiac gene expression and metabolism Hearts from Med13 alphaMHC transgenic mice and wild type littermates
2012-02-18 | E-GEOD-35902 | biostudies-arrayexpress
Project description:Timed matings were performed using C57BL/6 mice and pregnant females sacrificed starting at embryonic day (E) 10.5, and then in daily intervals until E14.5. Gene expression was be further analyzed at E16.5 and E18.5, to monitor changes in gene expression related to maturation of the heart. At stage 10.5, the rostral and caudal parts of the embryo were removed and the middle part, which includes the heart, was subjected to expression analysis. From embryonic day 11.5 on, we isolated embryonic hearts and separated the ventricular from the atrial chambers. Keywords = heart Keywords = development Keywords = cardiac Keywords: time-course
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