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.
Distinct hematopoietic stem cell subtypes are differentially regulated by TGF-beta1.
Sex, Specimen part
View SamplesDuring 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.
The Wnt3a/β-catenin target gene Mesogenin1 controls the segmentation clock by activating a Notch signalling program.
Specimen part, Treatment
View SamplesThe 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.
The Wnt3a/β-catenin target gene Mesogenin1 controls the segmentation clock by activating a Notch signalling program.
No sample metadata fields
View SamplesThe 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).
Activating the unfolded protein response in osteocytes causes hyperostosis consistent with craniodiaphyseal dysplasia.
Specimen part
View SamplesFoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis
FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis.
Cell line
View SamplesAdipose 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.
High-fat diet triggers inflammation-induced cleavage of SIRT1 in adipose tissue to promote metabolic dysfunction.
No sample metadata fields
View SamplesProliferative zone chondrocytes were microdissected from control and Ift88-deleted growth plates to determine gene expression profiles regulated by primary cilia.
Ift88 regulates Hedgehog signaling, Sfrp5 expression, and β-catenin activity in post-natal growth plate.
Specimen part
View SamplesDiet-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.
Effects of diurnal variation of gut microbes and high-fat feeding on host circadian clock function and metabolism.
Specimen part
View SamplesWe examined the effects of high-fat diet on feeding behaviour, body weight regulation and common biomarkers associated with weight gain in the C57BL/6J mice over a period of 10 weeks, making measurements at weeks 2, 4 and 10. We examined the transcriptomic profile of hepatic genes involved in the major lipid metabolic pathways, validating the key genes with quantitative real-time reverse-transcription PCR (qRT-PCR) and their gene products with western blots.
Sequential responses to high-fat and high-calorie feeding in an obese mouse model.
No sample metadata fields
View SamplesThe overall goal of this project is to investigate the role of TGF-beta signaling in tissue-tissue interactions between myogenic precursors of craniofacial muscles and cranial neural crest cells (CNCCs). Here, we conducted gene expression profiling of the tongue bud from mice at embryonic day E13.5 with a CNCC-specific conditional inactivation of the TGF-beta receptor type 1 gene Alk5. These mice provide a model of microglossia as well as disrupted extraocular and masticatory muscle development, which are congenital birth defects commonly observed in several syndromic conditions.
ALK5-mediated transforming growth factor β signaling in neural crest cells controls craniofacial muscle development via tissue-tissue interactions.
Sex, Specimen part
View Samples