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GSE16475
Mus musculus
6 Downloadable Samples
Description
The traditional view of hematopoiesis has been that all the cells of the peripheral blood are the progeny of a unitary homogeneous pool of hematopoietic stem cells (HSCs). Recent evidence suggests that the hematopoietic system is actually maintained by a consortium of HSC subtypes with distinct functional characteristics. We show here that myeloid-biased HSCs (My-HSCs) and lymphoid-biased (Ly-HSCs) can be purified according to their capacity for Hoechst dye efflux in combination with canonical HSC markers.
Publication Title
Distinct hematopoietic stem cell subtypes are differentially regulated by TGF-beta1.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 22 Downloadable Samples
Description
Recent genetic studies in mice have established a key role for the nuclear receptor coregulator Trim24 in liver tumor suppression and provided evidence that Trim24 suppresses hepatocarcinogenesis by inhibiting retinoic acid receptor alpha (Rara)-dependent transcription and cell proliferation. However, it is unknown which downstream targets of Rara regulated by Trim24 are critical for tumorigenesis. We report here that loss of Trim24 results in the overexpression of interferon (IFN)/STAT pathway genes in the liver, a process that occurs early in tumorigenesis and is more pronounced in tumors, despite the enhanced expression, late in the disease, of negative regulators such as Usp18, Socs1 and Socs2.
Publication Title
Tripartite motif 24 (Trim24/Tif1α) tumor suppressor protein is a novel negative regulator of interferon (IFN)/signal transducers and activators of transcription (STAT) signaling pathway acting through retinoic acid receptor α (Rarα) inhibition.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
Description
To test the regulatory effects of Dmrt5 on gene expression, we designed tetracycline inducible lines of Dmrt5 transgenic mouse ESCs. Overexpression of Dmrt5 was induced upon addition of Doxycycline (Dox). To evaluate the effects of Dmrt5 on gene expression in different stages of in vitro differentiated NPC derived from mouse embryonic stem cells (ESC), we analyzed gene expression profiles at differentiation day 7 and day 9 with or without Dox. The data revealed that overexpression of Dmrt5 in in vitro differentiated neural progenitor cells (NPC) regulates gene expression. Addition of Dox to the medium of the control cell line rtTA did not significantly alter gene expression profile, demonstrating that the observed effects were through induction of Dmrt5, but not simply through Dox.
Publication Title
Doublesex and mab-3-related transcription factor 5 promotes midbrain dopaminergic identity in pluripotent stem cells by enforcing a ventral-medial progenitor fate.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Diet-induced obesity (DIO) is rapidly becoming a global health problem, particularly as Westernization of emerging nations continues. Currently, one third of adult Americans are considered obese and, if current trends continue, >90% of US citizens are predicted to be affected by 2050. However, efforts to fight this epidemic have not yet produced sound solutions for prevention or treatment. Our studies reveal a balanced and chronobiological relationship between food consumption, daily variation in gut microbial evenness and function, basomedial hypothalamic circadian clock (CC) gene expression, and key hepatic metabolic regulatory networks , including CC and nuclear receptors (NR), that is are essential for metabolic homeostasis. Western diets high in saturated fats dramatically alter diurnal variation in microbial composition and function, which in turn lead to uncoupling of the hepatic CC and NR networks from central CC control in ways that offset the timing and types of regulatory factors directing metabolic function. These signals include microbial metabolites such as short chain fatty acids (SCFAs) and hydrogen sulfide (H2S) that can directly regulate or disrupt metabolic networks of the hepatocyte. Our study therefore provides insights into the complex and dynamic relationships between diet, gut microbes, and the host that are critical for maintenance of health. Perturbations of this constellation of processes, in this case by diet-induced dysbiosis and its metabolomic signaling, can potentially promote metabolic imbalances and disease. This knowledge opens up many possibilities for novel therapeutic and interventional strategies to treat and prevent DIO, ranging from the manipulation of gut microbial function to pharmacological targeting of host pathways to restore metabolic balance.
Publication Title
Effects of diurnal variation of gut microbes and high-fat feeding on host circadian clock function and metabolism.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
Description
Brain-derived serotonin favors appetite in mice following its binding to the Htr1a and Htr2b receptors in arcuate neurons of the hypothalamus. In this study, we identified that CREB is the transcriptional effector of brain-derived serotonin control of appetite in arcuate nuclei.
Publication Title
Leptin-dependent serotonin control of appetite: temporal specificity, transcriptional regulation, and therapeutic implications.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 17 Downloadable Samples
Description
During mammalian gastrulation, pluripotent epiblast stem cells migrate through the primitive streak to form the multipotent progenitors of the mesoderm and endoderm germ layers. Msgn1 is a bHLH transcription factor and is a direct target gene of the Wnt/bcatenin signaling pathway. Msgn1 is expressed in the mesodermal compartment of the primitive streak and is necessary for the proper development of the mesoderm. Msgn1 mutants show defects in somitogenesis leading to a lack of trunk skeletal muscles, vertebra and ribs.
Publication Title
The Wnt3a/β-catenin target gene Mesogenin1 controls the segmentation clock by activating a Notch signalling program.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 5 Downloadable Samples
Description
The goal of this project was to elucidate the target genes and transcriptional networks activated by Wnt3a during gastrulation, a complex morphogenetic process in which the embryonic germ layers are formed and the vertebrate body plan is established.
Publication Title
The Wnt3a/β-catenin target gene Mesogenin1 controls the segmentation clock by activating a Notch signalling program.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Description
The ectopic expression of a Col10a1-13del transgene in osteocytes induced ER stress, compromising their differentiation and expression of Sclerostin, resulting in generalized bone overgrowth resembling human crainodiaphyseal chondrodysplasia (CCD).
Publication Title
Activating the unfolded protein response in osteocytes causes hyperostosis consistent with craniodiaphyseal dysplasia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
Description
Progressive tissue fibrosis is a major cause of morbidity, and idiopathic pulmonary fibrosis (IPF) is a terminal illness characterized by unremitting matrix deposition in the lung with very limited choice of therapies. The imcomplete understanding of the mechanisms of progressive fibrosis curbs the progress in therapeutics development. Of which, the origin of fibrotic fibroblasts has been poorly defined during the pathogenesis of tissue fibrosis. Here, we fate-mapped a early embryonic transcription factor T-box gene 4 (Tbx4)-derived mesenchymal progenitors in injured adult lung and found that Tbx4+ lineage cells are the major source of myofibroblasts. The ablation of Tbx4+ cells or disruption of Tbx4 signaling attenuated lung fibrosis in bleomycin injury model in mice in vivo. Furthermore, Tbx4+ fibroblasts are more invasive and the regulation of fibroblast invasiveness by Tbx4 is through mediating hyaluronan synthase 2 (HAS2). This study identified a major mesenchymal transcription factor driving the development of fibrotic fibroblasts during lung fibrosis. Understanding the origin, signaling, and functions of these fibroblasts would prove pivotal in the development of therapeutics for patients with progressive fibrotic diseases.
Publication Title
Transcription factor TBX4 regulates myofibroblast accumulation and lung fibrosis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
Description
Adipose tissue plays an important role in storing excess nutrients and preventing ectopic lipid accumulation in other organs. Obesity leads to excess lipid storage in adipocytes, resulting in the generation of stress signals and the derangement of metabolic functions. SIRT1 is an important regulatory sensor of nutrient availability in many metabolic tissues. Here we report that SIRT1 functions in adipose tissue to protect from the development of inflammation and obesity under normal feeding conditions, and the progression to metabolic dysfunction under dietary stress. Genetic ablation of SIRT1 from adipose tissue leads to gene expression changes that highly overlap with changes induced by high fat diet in wild type mice, suggesting that dietary stress signals inhibit the activity of SIRT1. Indeed, we show that high fat diet induces the cleavage of SIRT1 in adipose tissue by the inflammation-activated caspase-1, providing a link between dietary stress and predisposition to metabolic dysfunction.
Publication Title
High-fat diet triggers inflammation-induced cleavage of SIRT1 in adipose tissue to promote metabolic dysfunction.
Sample Metadata Fields
No sample metadata fields
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