Polycomb group (PcG) proteins play a pivotal role in silencing developmental genes and help to maintain various stem and precursor cells and regulate their differentiation. PcG factors also regulate dynamic and complex regional specification, particularly in mammals, but this activity is mechanistically not well understood. In this study, we focused on proximal-distal (PD) patterning of the mouse forelimb bud to elucidate how PcG factors contribute to a regional specification process that depends on developmental signals. Depletion of the RING1 proteins RING1A (RING1) and RING1B (RNF2), which are essential components of Polycomb repressive complex 1 (PRC1), led to severe defects in forelimb formation along the PD axis. We show that preferential defects in early distal specification in Ring1A/B-deficient forelimb buds accompany failures in the repression of proximal signal circuitry bound by RING1B, including Meis1/2, and the activation of distal signal circuitry in the prospective distal region. Additional deletion of Meis2 induced partial restoration of the distal gene expression and limb formation seen in the Ring1A/B-deficient mice, suggesting a crucial role for RING1-dependent repression of Meis2 and likely also Meis1 for distal specification. We suggest that the RING1-MEIS1/2 axis is regulated by early PD signals and contributes to the initiation or maintenance of the distal signal circuitry.
RING1 proteins contribute to early proximal-distal specification of the forelimb bud by restricting Meis2 expression.
Specimen part
View SamplesPolycomb group (PcG) proteins play a pivotal role in silencing of development-related genes and contribute to maintain various stem and precursor cells and regulate their differentiation. However, it is not well understood how PcG factors regulate dynamic and complex morphogenetic processes particularly in mammals. In this study, we focused on proximal-distal (PD) patterning of forelimb bud to elucidate how PcG factors contribute to regulation of morphogenetic processes that depends on developmental signals. Depletion of RING1 proteins, which are common components of both canonical and variant Polycomb repressive complex-1 (PRC1), led to dramatic deficiencies in forelimb formation.
RING1 proteins contribute to early proximal-distal specification of the forelimb bud by restricting Meis2 expression.
Specimen part
View SamplesIschemia reperfusion injury (IRI) in organ transplantation remains a significant problem with limited alternative therapeutic options. Organs that undergo significant damage during IRI, particularly those enduring long warm ischemia times, undergo significant delayed graft function (DGF) after reperfusion and tend to have greater complications long term with the onset of chronic rejection. The gas molecule carbon monoxide (CO) has emerged as an agent that can suppress IRI in rodent models of solid organ transplantation. Since the use of CO is a potential therapeutic modality in humans, we tested if CO can prevent DGF in a pig model of kidney transplantation
Intraoperative administration of inhaled carbon monoxide reduces delayed graft function in kidney allografts in Swine.
Specimen part
View SamplesIron deficiency-induced anemia is generally a representative nutritional problem in most populations. We reported that the anemia due to dietary iron deficiency causes a variety of changes in nutrient metabolism, even leading to apoptosis as a result of associated endoplasmic reticulum (ER) stress in the rat liver. On the other hand, it appears that non-anemic iron-deficiency causes no serious problem because no appreciable down-regulation of hemoglobin synthesis occurs. Biochemically, iron is essential for activation of cytochrome-related enzymes and its deficiency should yield some physiological problems. We performed a comprehensive transcriptome analysis to define the effects of non-anemic iron deficiency on hepatic gene expression. Four-week-old rats were fed a low-iron diet (ca. 3 ppm iron) for 2 days. These rats were compared with those fed a control diet (48 ppm iron) by pair feeding. On day 3, the rats were sacrificed under anesthesia, and their livers were dissected for DNA microarray analysis. Rats in the iron-deficient diet group, showed that their serum ferritin and iron levels decreased with an increase in the serum total iron binding capacity (TIBC) level, while the hemoglobin level was not changed. In the DNA microarray study, we identified 91 up-regulated and 186 down-regulated probe sets that characterized the iron-deficient diet group. In the up-regulated probe sets, genes involved in glucose and lipid metabolic processes were significantly enriched, whereas genes related to organic acid metabolic process, cellular ketone metabolic process, lipid metabolic process, oxidation reduction, response to drug, response to extracellular stimulus and gas transport were significantly enriched in the down-regulated probe sets. These results suggest that even the non-anemic iron-deficiency exerts various influences on nutrient metabolisms in the liver.
Influence of a short-term iron-deficient diet on hepatic gene expression profiles in rats.
Sex, Age, Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Coordinated regulation of hepatic and adipose tissue transcriptomes by the oral administration of an amino acid mixture simulating the larval saliva of Vespa species.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Quantitative deviating effects of maple syrup extract supplementation on the hepatic gene expression of mice fed a high-fat diet.
Sex, Specimen part
View SamplesVAAM stands for an amino acid mixture simulating the composition of Vespa, a hornet larval saliva. We conducted a comparative study on metabolism-regulatory roles of VAAM, casein-simulating amino acid mixture (CAAM), and pure water on murine hepatic and adipose tissue transcriptomes. Mice were orally fed VAAM solution ( 0.675 g/ kg BW = 2% of food-derived amino acids = 0.38% of total food energy/ day), CAAM solution ( 0.675 g / kg BW/ day) or water under ad libitum for five days. Hepatic transcriptome comparison of VAAM, CAAM and water-treated groups revealed a VAAM-specific regulation of the metabolic pathway, i.e., the down-regulation of glycolysis and fatty acid oxidation, and up-regulation of poly unsaturated fatty acid synthesis and glycogenic amino acids utilization in TCA cycle. Similar transcriptomic analysis of white and brown adipose tissues (WAT and BAT) suggested the up-regulation of phospholipid synthesis in WAT and the negative regulation of cellular processes in BAT. Because these coordinated regulations of tissue transcriptomes implicated the presence of upstream signaling common to these tissues, we conducted Ingenuity Pathways Analysis of these transcriptomes with the results that estrogenic and glucagon signals seemed to be activated in liver and WAT as well as beta-adrenergic signaling did in the three tissues by administration of VAAM. Our data provide a clue to understanding the role of VAAM in metabolic regulation of multiple tissues.
Coordinated regulation of hepatic and adipose tissue transcriptomes by the oral administration of an amino acid mixture simulating the larval saliva of Vespa species.
Sex, Specimen part
View SamplesVAAM stands for an amino acid mixture simulating the composition of Vespa, a hornet larval saliva. We conducted a comparative study on metabolism-regulatory roles of VAAM, casein-simulating amino acid mixture (CAAM), and pure water on murine hepatic and adipose tissue transcriptomes. Mice were orally fed VAAM solution ( 0.675 g/ kg BW = 2% of food-derived amino acids = 0.38% of total food energy/ day), CAAM solution ( 0.675 g / kg BW/ day) or water under ad libitum for five days. Hepatic transcriptome comparison of VAAM, CAAM and water-treated groups revealed a VAAM-specific regulation of the metabolic pathway, i.e., the down-regulation of glycolysis and fatty acid oxidation, and up-regulation of poly unsaturated fatty acid synthesis and glycogenic amino acids utilization in TCA cycle. Similar transcriptomic analysis of white and brown adipose tissues (WAT and BAT) suggested the up-regulation of phospholipid synthesis in WAT and the negative regulation of cellular processes in BAT. Because these coordinated regulations of tissue transcriptomes implicated the presence of upstream signaling common to these tissues, we conducted Ingenuity Pathways Analysis of these transcriptomes with the results that estrogenic and glucagon signals seemed to be activated in liver and WAT as well as beta-adrenergic signaling did in the three tissues by administration of VAAM. Our data provide a clue to understanding the role of VAAM in metabolic regulation of multiple tissues.
Coordinated regulation of hepatic and adipose tissue transcriptomes by the oral administration of an amino acid mixture simulating the larval saliva of Vespa species.
Sex, Specimen part
View SamplesThe effects of the administration of maple syrup extract (MSXH) on hepatic gene expression were investigated in mice fed high-fat diet.
Quantitative deviating effects of maple syrup extract supplementation on the hepatic gene expression of mice fed a high-fat diet.
Sex, Specimen part
View SamplesThe effects of the administration of maple syrup extract (MSXH) on hepatic gene expression were investigated in mice fed high-fat diet.
Quantitative deviating effects of maple syrup extract supplementation on the hepatic gene expression of mice fed a high-fat diet.
Sex, Specimen part
View Samples