Obesity is a heterogeneous conditions comprising obese individuals with metabolic disorders (termed metabolically unhealthy obese; MUO) and obese individuals who are metabolically healthy (termed metabolically healthy obese; MHO).
Serum and adipose tissue amino acid homeostasis in the metabolically healthy obese.
Specimen part, Disease, Disease stage
View SamplesPurpose: Epidemiological and intervention studies have attempted to link the health effects of a diet rich in fruits and vegetables with the consumption of polyphenols and their impact in neurodegenerative diseases. Studies have shown that polyphenols can cross the intestinal barrier and reach concentrations in the bloodstream able to exert effects in vivo. However, the effective uptake of polyphenols in the brain is still regarded with some reservations. Here we describe a combination of approaches to examine the putative transport of blackberry-digested polyphenols (BDP) across the blood-brain barrier (BBB) and ultimate evaluation of their beneficial effects.
Blood-brain barrier transport and neuroprotective potential of blackberry-digested polyphenols: an in vitro study.
Sex, Specimen part, Cell line, Race
View SamplesCell fate perturbations underlie many human diseases, including breast cancer. However, the regulation of breast cell fate remains largely elusive. The mammary gland epithelium consists of differentiated luminal epithelial and basal myoepithelial cells, as well as undifferentiated stem cells and more restricted progenitors. Breast cancer originates from this epithelium but the molecular mechanisms underlying breast epithelial hierarchy remain ill-defined. Mouse and human luminal cells express keratins (K)18, 8, 19 and/or estrogen receptor (ER) and progesterone receptor (PR), their basal counterparts express K5, 14 and/or p63 and/or -smooth-muscle actin (-SMA)4-6. In this study, using a high-content confocal image-based shRNA screen for tumor suppressors regulating human breast cell fate, we discovered that ablation of the Hippo kinases large tumor suppressor (LATS) 1 and 2, promoted luminal fate and increased the number of bipotent and luminal progenitors, the proposed cell-of-origin of most human breast cancers. Mechanistically, we discovered a crosstalk between Hippo and ER signaling. In the presence of LATS, ER was targeted for ubiquitination and proteasomal degradation. Loss of LATS stabilized ER and Hippo effectors YAP/TAZ, which in concert control breast cell fate via intrinsic and paracrine mechanisms. Our findings uncover a novel non-canonical (i.e., YAP/TAZ-independent) effect of LATS in the regulation of human breast cell fate.
The Hippo kinases LATS1 and 2 control human breast cell fate via crosstalk with ERα.
Specimen part, Cell line
View SamplesPerturbation of the tightly regulated dynamic process of cell fate underlies many human diseases. The molecular mechanisms regulating breast cell fate in the hierarchically organized luminal and basal lineages of breast epithelium remain largely elusive. We performed a high-content confocal image-based shRNA screen for regulators of primary human breast cell fate. Inhibition of the Hippo kinases LATS was found to promote luminal fate and increase the number of progenitors, which is a paradox given that Hippo effectors YAP/TAZ have been associated with basal fate. Mechanistically, LATS loss increases the activities of YAP/TAZ and ER, which in concert control breast cell fate via intrinsic and paracrine effects. Reduced LATS expression is found in breast cancers with a poor prognosis; this diminishes the sensitivity of ER-positive- and increases the sensitivity of ER-negative cancers to endocrine therapy. Thus, in this study we have unraveled crosstalk between Hippo and estrogen signaling and shown that LATS loss triggers expansion of luminal progenitors, the highly suspected cell-of-origin in most breast cancers.
The Hippo kinases LATS1 and 2 control human breast cell fate via crosstalk with ERα.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
PIK3CA(H1047R) induces multipotency and multi-lineage mammary tumours.
Specimen part, Treatment
View SamplesThis study examined the effect of early pregnancy on the gene expression profiles of stromal and various epithelial mammary cell subpopulations in mice.
PIK3CA(H1047R) induces multipotency and multi-lineage mammary tumours.
Specimen part
View SamplesThis study examined the gene expression profile of mammary tumors derived from Lgr5- and K8-positive cell-of-origins
PIK3CA(H1047R) induces multipotency and multi-lineage mammary tumours.
Specimen part
View SamplesThis study examined the effect of mutant PIK3CAH1047R expression in mammary subsets of preneoplastic mammary glands from Lgr5-creERT2/PIK3CA H1047R mice
PIK3CA(H1047R) induces multipotency and multi-lineage mammary tumours.
Specimen part, Treatment
View SamplesThis study examined the effect of mutant PIK3CAH1047R expression in mammary subsets of preneoplastic mammary glands from K8-creERT2/PIK3CA H1047R mice
PIK3CA(H1047R) induces multipotency and multi-lineage mammary tumours.
Treatment, Time
View SamplesBcl11b plays an important role in postnatal dentate gyrus development and adult neurogenesis. To determine its role in adult neurogenesis independant from postnatal development the Bcl11b mutation was induced at the age of 2 months.
Stability and Function of Hippocampal Mossy Fiber Synapses Depend on <i>Bcl11b/Ctip2</i>.
Specimen part
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