Obesity has emerged as a formidable health crisis due to its association with metabolic risk factors such as diabetes, dyslipidaemia and hypertension. Recent work has demonstrated the multifaceted roles of lncRNAs in regulating mouse adipose development, but its implication in human adipocytes remain largely unknown at least partially due to the lack of a comprehensive lncRNA catalog, particularly those specifically expressed in brown adipose tissue (BAT). In this study, we performed deep RNA-seq on adult subcutaneous, omental and fetal brown adipose tissues to de novo construct a catalog of 3,149 adipose active lncRNAs of which 1,351 are specifically detected in BAT. We further identified 318 lncRNAs conserved between human and mouse which, compared with non-conserved ones, are more broadly expressed in multiple cell types. One of these, lnc-dPRDM16, is transcribed divergently from Prdm16, tightly correlated with Prdm16 (R = 0.7) in both mouse and human, and co-expressed (R = 0.7) with protein-coding genes enriched in lipid and fatty acid catabolic processes. Loss of function of lnc-dPRDM16 led to a down-regulation of Prdm16 and an obvious reduction of adipogenesis in brown adipocyte culture. Together, our work has provided a comprehensive human adipose catalog built from diverse fat types, which when applied to our roadmap, identifies lnc-dPRDM16 as a promising modulator of adipose development for future clinical research. Overall design: Transcriptome profiling of BAT, OME and SUB samples
De novo reconstruction of human adipose transcriptome reveals conserved lncRNAs as regulators of brown adipogenesis.
Specimen part, Subject
View SamplesPurpose: Determine the function of lncBATE10 in brown and white adipocyte differentiation Methods: primary brown and white apreadipocytes were isolated by cell culture. We infected brown preadipocytes with retroviral shRNA targeting lncBATE10 or with retrovirus overexpressing lncBATE10. Cells were induced to differetinate for 5 days. Total RNA were harvested for RNA-seq Conclusions: Our study shows that lncBATE10 is required for BAT-selective program expression. Overexpression of lncBATE10 is not sufficient to promote BAT marker expression. Overall design: total RNAs from primary brown and white adipocytes cultures (sh-control, shRNA knockdown, overexpression vector, overexpression of lncBATE10) were generated by deep sequencing using Hi-seq 2000
Dynamic transcriptome changes during adipose tissue energy expenditure reveal critical roles for long noncoding RNA regulators.
Specimen part, Cell line, Treatment, Subject
View SamplesE-cadherin (E-cad) mediates cell-cell adhesion and has been proposed to suppress both invasion and metastasis. However, invasive ductal cancers retain E-cad expression in the primary tumor, circulating tumor cells, and distant metastases. We recently demonstrated that cancer cell clusters are efficient metastatic seeds. Since clusters organize through cell-cell adhesion, we tested the requirement for E-cad in genetically engineered mouse models of luminal and basal breast cancer. Loss of E-cad increased invasion and dissemination in 3D culture and in the mammary gland. However, E-cad loss also reduced cancer cell proliferation, survival, tumor cell seeding, and metastatic outgrowth in the lungs. At the transcript level, loss of E-cad was associated with increased apoptosis. Consistent with these results, inhibition of apoptosis partially rescued the metastatic phenotype of E-cad null cancer cells. We therefore propose that E-cad is an invasion suppressor, survival factor, and metastasis promoter in invasive ductal cancers. Overall design: Differential gene expression analysis between organoids isolated from adeno-Cre transduced MMTV-PyMT E-cad+/+ (r = 4 biological replicates) and adeno-Cre transduced MMTV-PyMT E-cadfl/fl (r = 5 biological replicates)
E-cadherin is required for metastasis in multiple models of breast cancer.
Specimen part, Cell line, Treatment, Subject
View SamplesThe tyrosine kinase receptors HER2 and HER3 play an important role in breast cancer. The HER2/HER3 heterodimer is a critical oncogenic unit associated with reduced relapse-free and decreased overall survival. We provide gene expression profile of the mammary epithelial cells MCF10A expressing HER2, HER3 or HER2/HER3 and grown in three-dimensional cultures for 15 days in the presence of heregulin, a known HER3-ligand that stabilizes and activates the HER2/HER3 heterodimer.
Co-expression of HER2 and HER3 receptor tyrosine kinases enhances invasion of breast cells via stimulation of interleukin-8 autocrine secretion.
Cell line
View SamplesExpression data from xenograft in BALB/c 6-wk-old nude mice with PC3 prostate cancer cells stably expressing PML or a vector control after treatment of the mice with palbociclib (100mg/kg/day diluted in sodium lactate 50mM pH4 given by gavage) during 5 consecutive days
A CDK4/6-Dependent Epigenetic Mechanism Protects Cancer Cells from PML-induced Senescence.
Specimen part, Cell line
View SamplesThe Epidermal Growth Factor Receptor 2 (ERBB2 or HER2) is amplified and overexpressed in approximately 20% of invasive breast cancers and is associated with metastasis and poor prognosis. Here we describe the role of a constitutively active splice variant of HER2 (Delta-HER2) in human mammary epithelial cells. Overexpression of Delta-HER2 in human mammary cells decreased apoptosis and increased proliferation and expression of epithelial-to-mesenchymal markers. It also induced invasion in three-dimensional cultures and promoted tumorigenicity and metastasis in vivo. In contrast, similar overexpression of wild-type HER2 failed to evoke the same effects. Unbiased protein-tyrosine phosphorylation profiling revealed a significant increase in phosphorylation of several key signaling proteins upon Delta-HER2 expression, some of which not previously shown to belong to the HER2 pathway. In addition, microarray analysis revealed the expression of a set of genes specifically associated with Delta-HER2 expression. We found those genes to be highly expressed in ER-negative, high grade and metastatic primary breast tumors. Altogether, these results provide new insights into the function of a tumorigenic splice variant of HER2 and the signaling cascade deriving from its activity
Mammary tumor formation and metastasis evoked by a HER2 splice variant.
Cell line
View SamplesA suggested role for fibrillr collagen topology in the pregnancy-induced protection and invasive phenotype.
Collagen architecture in pregnancy-induced protection from breast cancer.
Cell line
View SamplesUsing whole genome microarray (Affymetrix ATH1) we studied the transcriptional response of Arabidopsis thaliana to imidazolinone (Arsenal) herbicde that inhibits acetolactate synthase (ALS) enzyme and thus disrupts branched chain amino acid biosynthesis. A number of genes related to amino acid, protein metabolism, growth, regulatory networks, respiratory pathways, stress, defense and secondary metabolism were altered.
A composite transcriptional signature differentiates responses towards closely related herbicides in Arabidopsis thaliana and Brassica napus.
No sample metadata fields
View SamplesUsing whole genome microarray (Affymetrix ATH1) we studied the transcriptional response of Arabidopsis thaliana to glyphosate (Roundup Original) herbicde that inhibits 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) enzyme and thus disrupts aromaticamino acid biosynthesis. Few genes related to defense and secondary metabolism were altered.
A composite transcriptional signature differentiates responses towards closely related herbicides in Arabidopsis thaliana and Brassica napus.
No sample metadata fields
View SamplesUsing whole genome microarray (Affymetrix ATH1) we studied the transcriptional response of Arabidopsis thaliana to primisulfuron (Beacon) herbicde that inhibits acetolactate synthase (ALS) enzyme and thus disrupts branmched chain amino acid biosynthesis. A number of genes related to amino acid, protein metabolism, growth, regulatory networks, respiratory pathways, stress, defense and secondary metabolism were altered.
A composite transcriptional signature differentiates responses towards closely related herbicides in Arabidopsis thaliana and Brassica napus.
No sample metadata fields
View Samples