The Forkhead family of transcription factors comprises numerous members and is implicated in various cellular functions, including cell growth, apoptosis, migration and differentiation.In this study we identified the Forkhead factor FoxQ1 as increased in expression during TGF-beta1 induced changes in epithelial differentiation, suggesting functional roles of FoxQ1 for epithelial plasticity.The repression of FoxQ1 in mammary epithelial cells led to a change in cell morphology characterized by an increase in cell size, pronounced cell-cell contacts and an increased expression of several junction proteins (e.g. E-cadherin). In addition, FoxQ1 knock-down cells revealed rearrangements in the actin-cytoskeleton and slowed down cell cycle G1-phase progression.Furthermore, repression of FoxQ1 enhanced the migratory capacity of coherent mammary epithelial cells.Gene expression profiling of NM18 cells indicated that FoxQ1 is a relevant downstream mediator of TGF-beta1 induced gene expression changes. This included the differential expression of transcription factors involved in epithelial plasticity, e.g. Ets-1, Zeb1 and Zeb2.In summary, this study has elucidated the functional impact of FoxQ1 on epithelial differentiation
The Forkhead factor FoxQ1 influences epithelial differentiation.
Specimen part, Treatment
View SamplesThe presence of different types of immune cells in adipose tissue has been demonstrated in numerous studies. Whereas cells of the immune system in white adipose tissue contribute to the low-grade chronic inflammation under obese conditions, their function in brown adipose tissue (BAT) remains largely elusive. Here we report a role of regulatory T (Treg) cells in BAT physiology.Ablation of Treg cells resulted in massive invasion of macrophages into BAT concordant with rearrangement of BAT morphology. Treg ablated animals displayed reduced energy expenditure. Our results for the first time demonstrate a functional role of Treg cells in the regulation of energy homeostasis.
Brown adipose tissue harbors a distinct sub-population of regulatory T cells.
Treatment
View SamplesLipid mobilization (lipolysis) in white adipose tissue (WAT) critically controls lipid turnover and adiposity in humans. While the acute regulation of lipolysis has been studied in detail, the transcriptional determinants of WAT lipolytic activity remain still largely unexplored. Here we show that the genetic inactivation of transcriptional co-factor transducin beta-like-related (TBLR) 1 blunts the lipolytic response of white adipocytes through the impairment of cAMP-dependent signal transduction. Indeed, mice lacking TBLR1 in adipocytes are defective in fasting-induced lipid mobilization and when placed on a high fat diet show aggravated adiposity, glucose intolerance and insulin resistance. TBLR1 levels are found to increase under lipolytic conditions in WAT of both human patients and mice, correlating with serum free fatty acids (FFA). As a critical regulator of WAT cAMP signaling and lipid mobilization, proper activity of TBLR1 in adipocytes may thus represent a critical molecular checkpoint for the prevention of metabolic dysfunction in subjects with obesity-related disorders.
Transcriptional cofactor TBLR1 controls lipid mobilization in white adipose tissue.
Specimen part, Treatment
View SamplesTo explore the molecular basis for TSC22D4 function in hepatic lipid homeostasis in vivo TSC22D4 was knocked down in the mouse liver using adenovirus and performed genome wide expression analysis.
TSC22D4 is a molecular output of hepatic wasting metabolism.
Specimen part
View SamplesMost human cancers present hyperactivated sumoylation, and cancer cell lines are usually highly sensitive to the lack of it, supporting potential application of sumoylation chemical inhibitors in cancer therapy. Here, we explored the impact of hyposumoylation (Ubc9 haploinsufficiency) on cancer development in mice using Apc loss-driven intestinal tumorigenesis model.
An unanticipated tumor-suppressive role of the SUMO pathway in the intestine unveiled by Ubc9 haploinsufficiency.
Specimen part
View SamplesThe Lgr5+ intestinal stem cell, Paneth and transit-amplifying cell compartment constitute the intestinal crypt which is the constant source of differentiated epithelial cells that replenish the intestinal villi ensuring organ maintenance and regeneration. The Lgr5+ crypt-based columnar (CBC) cells have been identified as the intestinal stem cells (ISCs) and, importantly, as cells-of-origin of intestinal cancer.
An unanticipated tumor-suppressive role of the SUMO pathway in the intestine unveiled by Ubc9 haploinsufficiency.
Specimen part
View SamplesComparative RNA profiling between tumor cells and their secreted extracellular vesicles. Results revealed enrichment in genes involved in cellular migration and metastasis in extracellular vesicles, in agreement with their role as mediators of tumor progression.
In Vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior.
Cell line
View SamplesExpression levels of the RNA-binding protein Quaking (QKI) are low in monocytes of early, human atherosclerotic lesions, but abundant in macrophages of advanced plaques. Specific depletion of QKI protein impaired monocyte adhesion, migration, differentiation into macrophages, and foam cell formation in vitro and in vivo. RNA-seq and microarray analysis of human monocyte and macrophage transcriptomes, including those of a unique QKI haploinsufficient patient, revealed striking changes in QKI-dependent mRNA levels and splicing of RNA transcripts. Overall design: RNA-seq analysis of primary monocytes and macrophages from a QKI haploinsufficient patient and their (control) sibling.
Quaking promotes monocyte differentiation into pro-atherogenic macrophages by controlling pre-mRNA splicing and gene expression.
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