Selective enrichment of founding reproductive microbiomes allows extensive vertical transmission in a fungus-farming termite

Mutualistic coevolution can be mediated by vertical transmission of symbionts between host generations. Termites host complex gut bacterial communities with evolutionary histories indicative of mixed-mode transmission. Here, we document that vertical transmission of gut bacterial strains is congruent across parent to offspring colonies in four pedigrees of the fungus-farming termite Macrotermes natalensis. We show that 44% of the offspring colony microbiome, including more than 80 bacterial genera and pedigree-specific strains, are consistently inherited. We go on to demonstrate that this is achieved because colony-founding reproductives are selectively enriched with a set of non-random, environmentally sensitive and termite-specific gut microbes from their colonies of origin. These symbionts transfer to offspring colony workers with high fidelity, after which priority effects appear to influence the composition of the establishing microbiome. Termite reproductives thus secure transmission of complex communities of specific, co-evolved microbes that are critical to their offspring colonies. Extensive yet imperfect inheritance implies that the maturing colony benefits from acquiring environmental microbes to complement combinations of termite, fungus and vertically transmitted microbes; a mode of transmission that is emerging as a prevailing strategy for hosts to assemble complex adaptive microbiomes. </p

The orphan nuclear receptor COUP-TFII coordinates hypoxia-independent proangiogenic responses in hepatic stellate cells

BACKGROUND & AIMS: Hepatic stellate cell (HSC) transdifferentiation into collagen-producing myofibroblasts is a key event in hepatic fibrogenesis, but the transcriptional network that controls the acquisition of the activated phenotype is still poorly understood. In this study, we explored whether the nuclear receptor chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) is involved in HSC activation and in the multifunctional role of these cells during the response to liver injury. METHODS: COUP-TFII expression was evaluated in normal and cirrhotic livers by immunohistochemistry and Western blot. The role of COUP-TFII in HSC was assessed by gain and loss of function transfection experiments and by generation of mice with COUP-TFII deletion in HSC. Molecular changes were determined by gene expression microarray and RT-qPCR. RESULTS: We showed that COUP-TFII is highly expressed in human fibrotic liver and in mouse models of hepatic injury. COUP-TFII expression rapidly increased upon HSC activation and it was associated with the regulation of genes involved in cell motility, proliferation and angiogenesis. Inactivation of COUP-TFII impairs proliferation and invasiveness in activated HSC and COUP-TFII deletion in mice abrogate HSC activation and angiogenesis. Finally, co-culture experiments with HSC and liver sinusoidal endothelial cells (SEC) showed that COUP-TFII expression in HSC influenced SEC migration and tubulogenesis via a hypoxia-independent and nuclear factor κB-dependent mechanism. CONCLUSION: This study elucidates a novel transcriptional pathway in HSC that is involved in the acquisition of the proangiogenic phenotype and regulates the paracrine signals between HSC and SEC during hepatic wound healing. LAY SUMMARY: In this study, we identified an important regulator of HSC pathobiology. We showed that the orphan receptor COUP-TFII is an important player in hepatic neoangiogenesis. COUP-TFII expression in HSC controls the crosstalk between HSC and endothelial cells coordinating vascular remodelling during liver injury. TRANSCRIPT PROFILING: ArrayExpress accession E-MTAB-1795

Glucose-Dependent Regulation of NR2F2 Promoter and Influence of SNP-rs3743462 on Whole Body Insulin Sensitivity

Background: The Nuclear Receptor 2F2 (NR2F2/COUP-TFII) heterozygous knockout mice display low basal insulinemia and enhanced insulin sensitivity. We previously established that insulin represses NR2F2 gene expression in pancreatic β-cells. The cis-regulatory region of the NR2F2 promoter is unknown and its influence on metabolism in humans is poorly understood. The present study aimed to identify the regulatory regions that control NR2F2 gene transcription and to evaluate the effect of NR2F2 promoter variation on glucose homeostasis in humans. Methodology/Principal Findings: Regulation of the NR2F2 promoter was assessed using gene reporter assays, ChIP and gel shift experiments. The effects of variation at SNP rs3743462 in NR2F2 on quantitative metabolic traits were studied in two European prospective cohorts. We identified a minimal promoter region that down-regulates NR2F2 expression by attenuating HNF4α activation in response to high glucose concentrations. Subjects of the French DESIR population, who carried the rs3743462 T-to-C polymorphism, located in the distal glucose-responsive promoter, displayed lower basal insulin levels and lower HOMA-IR index. The C-allele at rs3743462 was associated with increased NR2F2 binding and decreased NR2F2 gene expression. Conclusions/Significance: The rs3743462 polymorphism affects glucose-responsive NR2F2 promoter regulation and thereby may influence whole-body insulin sensitivity, suggesting a role of NR2F2 in the control of glucose homeostasis in humans. © 2012 Boutant et al

The Nutritional Induction of COUP-TFII Gene Expression in Ventromedial Hypothalamic Neurons Is Mediated by the Melanocortin Pathway

BACKGROUND: The nuclear receptor chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) is an important coordinator of glucose homeostasis. We report, for the first time, a unique differential regulation of its expression by the nutritional status in the mouse hypothalamus compared to peripheral tissues. METHODOLOGY/PRINCIPAL FINDINGS: Using hyperinsulinemic-euglycemic clamps and insulinopenic mice, we show that insulin upregulates its expression in the hypothalamus. Immunofluorescence studies demonstrate that COUP-TFII gene expression is restricted to a subpopulation of ventromedial hypothalamic neurons expressing the melanocortin receptor. In GT1-7 hypothalamic cells, the MC4-R agonist MTII leads to a dose dependant increase of COUP-TFII gene expression secondarily to a local increase in cAMP concentrations. Transfection experiments, using a COUP-TFII promoter containing a functional cAMP responsive element, suggest a direct transcriptional activation by cAMP. Finally, we show that the fed state or intracerebroventricular injections of MTII in mice induce an increased hypothalamic COUP-TFII expression associated with a decreased hepatic and pancreatic COUP-TFII expression. CONCLUSIONS/SIGNIFICANCE: These observations strongly suggest that hypothalamic COUP-TFII gene expression could be a central integrator of insulin and melanocortin signaling pathway within the ventromedial hypothalamus. COUP-TFII could play a crucial role in brain integration of circulating signal of hunger and satiety involved in energy balance regulation

COUP-TFII Controls Mouse Pancreatic β-Cell Mass through GLP-1-β-Catenin Signaling Pathways

Background: The control of the functional pancreatic beta-cell mass serves the key homeostatic function of releasing the right amount of insulin to keep blood sugar in the normal range. It is not fully understood though how beta-cell mass is determined

Le facteur de transcription COUP-TFII hypothalamique (un nouvel acteur dans le contrôle de l'homéostasie énergétique)

Notre équipe travaille sur le facteur de transcription COUP-TFII. Le but de cette thèse est de comprendre le rôle de COUP-TFII dans l'hypothalamus et surtout son implication dans le maintien de l'homéostasie énergétique.Par immunofluorescence, nous avons observé que l'expression de la protéine COUP-TFII chez la souris est limitée au noyau ventromédian de l'hypothalamus (VMH). Il est présent dans des neurones exprimant le récepteur à la mélanocortine MC4-R, cellules impliquées dans l'homéostasie énergétique et co-localise avec la protéine SF1, un marqueur du noyau ventromédian. Pour étudier la fonction de ce facteur, nous avons généré une lignée de souris inactivées pour le gène COUP-TFII dans les neurones SF1 de l'hypothalamus, Les premiers résultats indiquent que les souris présentent un défaut de sensibilité à l'insuline, ces souris sont insulino-hyersensible. Nous étudions la régulation de l'expression de COUP-TFII en réponse à l'état nutritionnel et hormonal sur des modèles de souris différents. Une augmentation de l'insuline in vivo active l'expression des messagers COUP-TFII dans l'hypothalamus. Cependant, l'étude de sa régulation dans une lignée cellulaire dérivée de l'hypothalamus suggère fortement que les effets de l'insuline sur l'expression de COUP-TFII pourraient être indirectement liés à la production locale de ligand du récepteur MC-4R. Des expériences in vivo et ex vivo (par ICV) en utilisant un agoniste de la MC-4R ont montré une augmentation de l'expression des messagers COUP-TFII. Nos données nous permettent de poser est hypothalamus COUP-TFII comme un nouvel acteur impliqué dans le contrôle de la régulation de l'homéostasie énergétique.PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Fonction et régulation du facteur de transcription COUP-TFII dans les cellules b du pancréas

PARIS5-BU Méd.Cochin (751142101) / SudocSudocFranceF

Le facteur de transcription COUP-TFII, un nouvel acteur dans le contrôle de l'homéostasie glucidique dans le foie et le pancréas

La régulation de l'homéostasie glucidique est notamment contrôlée au niveau génique. Nous avions montré que la délétion de COUP-TFII (Chicken ovalbumin upstream promoter transcription factor II) dans les cellules insuliniques chez la souris entraîne un défaut de sécrétion d'insuline. Ce travail montre que 1) l'expression de COUP-TFII est contrôlée négativement par le glucose et l'insuline dans les cellules bêta du pancréas et les hépatocytes in vivo et in vitro via la signalisation des facteurs ChREBP et Foxo-1; 2) COUP-TFII inhibe la transcription, le contenu et la sécrétion d'insuline et Festérifïcation des acides gras dans la lignée de cellules bêta INS-1 832/13; 3) il existe une activation réciproque entre l'expression des gènes COUP-TFII et HNF-4a (MODY-1) dans les cellules bêta. Ces résultats permettent de proposer COUP-TFII comme une acteur majeur dans le contrôle de l'homéostasie glucidique à jeun, et donc potentiellement dans des pathologies comme le diabète de type 2.Metabolic pathways concerned in the regulation of glucose homeostasis in liver and pancreas are precisely controlled at gene level. We showed that COUP-TFII (Chicken ovalbumin upstream promoter transcription factor II) deletion from pancreatic beta cells in heterozygous mice led to abnormal insulin secretion. This work reveals that 1) COUP-TFII expression is negatively controlled by glucose and insulin in pancreatic beta cells and hepatocytes, in vivo and in vitro, via ChREBP and Foxo-1 signaling; 2) COUP-TFII inhibates insulin genes transcription, as well as insulin content and insulin secretion in beta 832/13 ENS-1 cell line, and decreases the fatty acid esterification capacity in these cells; 3) COUP-TFII and HNF-4alpha (MODY-1) activate one another their expression in pancreatic beta cells. These results conduct and argue to propose an important contribution of COUP-TFII hi the control of glucose homeostasis in the fasted state, and potentially in pathologies as type 2 diabetes.PARIS5-BU Méd.Cochin (751142101) / SudocSudocFranceF

Termite graveyards. Hidden geochemical patches?

International audienceEntombment, or the production of graveyards for the disposal of dead bodies, is not only a practice of human societies but is also observed in nature, including among small invertebrates such as termites. While the influence of termites on soil dynamics has largely been studied in comparing the specific properties of their mounds and protective sheeting with those of the surrounding soil, the properties of their graveyards have never been described before. Using incipient colonies of Macrotermes natalensis reared in a controlled environment, we showed that graveyard sheeting was characterized by a much higher C content in comparison with the reference soil and protective sheeting (4.7-fold increase). As a consequence, a slight increase in the C:N ratio was measured from 8 in the reference soil to 10 in graveyard sheeting. No changes in soil particle size fractions were measured. However, lower Fe and Al contents were measured in sheeting, and micrographs obtained from scanning electron microscopy revealed the presence of calcium carbonate, or calcium oxalate crystals, in sheeting, as well as the presence of organic substances and salt crystals covering termite corpses, most likely for controlling the spread of pathogens. The presence of calcium carbonates and/or calcium oxalate was explained by the very high Ca content within termite bodies. Therefore, this study shows that termite graveyards are likely to constitute unexplored patches of nutrients in soil

The role of the glucose-sensing transcription factor carbohydrate-responsive element-binding protein pathway in termite queen fertility.

International audienceTermites are among the few animals that themselves can digest the most abundant organic polymer, cellulose, into glucose. In mice and Drosophila, glucose can activate genes via the transcription factor carbohydrate-responsive element-binding protein (ChREBP) to induce glucose utilization and de novo lipogenesis. Here, we identify a termite orthologue of ChREBP and its downstream lipogenic targets, including acetyl-CoA carboxylase and fatty acid synthase. We show that all of these genes, including ChREBP, are upregulated in mature queens compared with kings, sterile workers and soldiers in eight different termite species. ChREBP is expressed in several tissues, including ovaries and fat bodies, and increases in expression in totipotent workers during their differentiation into neotenic mature queens. We further show that ChREBP is regulated by a carbohydrate diet in termite queens. Suppression of the lipogenic pathway by a pharmacological agent in queens elicits the same behavioural alterations in sterile workers as observed in queenless colonies, supporting that the ChREBP pathway partakes in the biosynthesis of semiochemicals that convey the signal of the presence of a fertile queen. Our results highlight ChREBP as a likely key factor for the regulation and signalling of queen fertility