The transition to lactation challenges dairy cows metabolically. Immune dysfunction and infectious disease risk is the hallmark of this transition period. Transcriptome data of PBMC shows differentially expressed pathways postpartum. Metabolically stressed cows show upregulation of innate immune pathways and inflammation. Overall design: Gene expression profiling of PMBCs from 6 dairy cows, each sampled 21 days prepartum and 7 days postpartum. Three cows (H1-3) showed signs of increased metabolic stress (by other assays) relative to the other three cows (L1-3).
The degree of postpartum metabolic challenge in dairy cows is associated with peripheral blood mononuclear cell transcriptome changes of the innate immune system.
Specimen part, Subject
View SamplesThe benefit of treatment in mild to moderate cases of E. coli mastitis in dairy cows remains a topic of discussion.
Impact of intramammary treatment on gene expression profiles in bovine Escherichia coli mastitis.
Treatment, Time
View SamplesObjective: Microarray analysis was used to determine the molecular mechanism underlying Fancd2 and Foxo3a double knockout mice HSCs exhaustion.
Fancd2 is required for nuclear retention of Foxo3a in hematopoietic stem cell maintenance.
Specimen part
View SamplesMacrophages represent an important component of the tumor microenvironment and play a complex role in cancer progression. These cells are characterized by a high degree of plasticity, and alter their phenotype in response to local environmental cues. While the M1/M2 classification of macrophages has been widely used, the complexity of macrophage phenotypes specifically in lung cancer has not been well studied. In this study we employed an orthotopic immunocompetent model of lung adenocarcinoma in which murine lung cancer cells are directly implanted into the left lobe of syngeneic mice. Using multi-marker flow cytometry we defined and recovered several distinct populations of monocytes/macrophages from tumors at different stages of progression. We used RNA-seq transcriptional profiling to define distinct features of each population and determine how they change during tumor progression. We defined an alveolar resident macrophage population that does not change in number and express multiple genes related to lipid metabolism and lipid signaling. We also defined a population of tumor-associated macrophages that increase dramatically with tumor, and selectively express a panel of chemokines genes. A third population, which resembles tumor-associated monocytes, expresses a large number of genes involved in matrix remodeling. By correlating transcriptional profiles with clinically prognostic genes, we show that specific monocyte/macrophage populations are enriched in genes that predict good or poor outcome in lung adenocarcinoma, implicating these subpopulations as critical determinants of patient survival. Our data underscore the complexity of monocytes/macrophages in the tumor microenvironment, and suggest that distinct populations play specific roles in tumor progression. Overall design: mRNA profiles of macrophage/monocyte cells isolated from murine control or tumor-bearing lung. From naive mice: MacA cells (MacA-N), MacB1 cells (MacB1-N), MacB2 cells (MacB2-N); from 2 week tumor bearing mice: MacA cells (MacA-2wk), MacB2 cells (MacB2-2wk), MacB3 cells (MacB3-3wk); from 3-week tumor bearing mice: MacB2 (MacB2-3wk), MacB3 cells (MacB3-3wk). Each population was analyzed in triplicate (cells were isolated in 3 independent experiments).
Expression Profiling of Macrophages Reveals Multiple Populations with Distinct Biological Roles in an Immunocompetent Orthotopic Model of Lung Cancer.
Cell line, Subject
View SamplesTranscription profiling by array of pancreas from KrasG12D, Ela-Tgfa and KrasG12D Ela-Tgfa mice
Concomitant pancreatic activation of Kras(G12D) and Tgfa results in cystic papillary neoplasms reminiscent of human IPMN.
Age, Specimen part
View SamplesSphingosine 1-phosphate (S1P) is a bioactive lipid whose levels are tightly regulated by its synthesis and degradation. Intracellularly, S1P is dephosphoryled by the actions of two S1P-specific phosphatases, sphingosine 1-phosphate phosphatase 1 and 2. To identify the physiologic functions of S1P phosphatase 1, we have studied mice with its gene, Sgpp1, deleted. Sgpp1-/- mice appeared normal at birth but during the first week of life, they exhibited stunted growth, suffered desquamation, and most died before weaning. Interestingly, the epidermal permeability barrier developed normally during embryogenesis. Sgpp1 -/- pups and surviving adults exhibited epidermal hyperplasia and abnormal expression of keratinocyte differentiation markers. Keratinocytes isolated from Sgpp1 -/- skin had increased intracellular S1P levels, and expressed a gene expression profile that indicated enhanced differentiation. The results reveal S1P metabolism as a regulator of keratinocyte differentiation and epidermal homeostasis.
Sphingosine-1-phosphate phosphatase 1 regulates keratinocyte differentiation and epidermal homeostasis.
Specimen part
View SamplesGene expression profile based classification of colonic diseases are suitable for identification of diagnostic mRNA expression patterns which can establish the basis of a new molecular biological diagnostic method
Diagnostic mRNA expression patterns of inflamed, benign, and malignant colorectal biopsy specimen and their correlation with peripheral blood results.
No sample metadata fields
View SamplesThe whole-genome oligonucleotide microarray analysis of peripheral blood samples can contribute to the determination of distant blood markers of local pathophysiological alterations in colorectal diseases. These markers can lead to alternative screening procedures.
Diagnostic mRNA expression patterns of inflamed, benign, and malignant colorectal biopsy specimen and their correlation with peripheral blood results.
No sample metadata fields
View SamplesAim: Differentiation of cardiac fibroblasts (Fb) into myofibroblasts (MyoFb) is responsible for connective tissue buildup in myocardial remodeling. We examined reversibility of MyoFb differentiation. Methods and Results: Adult rat cardiac Fb were cultured on a plastic substratum providing mechanical stress, with conditions to obtain different Fb phenotypes. Fb spontaneously differentiated to proliferating MyoFb (p-MyoFb) with stress fiber formation decorated with alpha-smooth muscle actin (-SMA). Transforming growth factor-1 (TGF-1) promoted terminal differentiation into -SMA positive MyoFb showing near absence of proliferation i.e. non-p-MyoFb (2-fold increase in cell number after 12 days vs 11-fold for p-MyoFb). SD-208, a TGF--receptor-I kinase blocker, inhibited p-MyoFb differentiation as shown by stress fiber absence, low levels of -SMA protein expression, and high levels of proliferation (32-fold increase after 12 days). Fb seeded in collagen matrices induced no contraction, whereas p-MyoFb and non-p-MyoFb induced 2.5- and 4-fold contraction. Fb produced low levels of collagen and secreted high levels of IL-10. Non-p-MyoFb showed high collagen production and high MCP-1 and TIMP-1 secretion. Transcriptome analysis indicated differential gene expression between all phenotypes. Dedifferentiation of p-MyoFb, but not of non-p-MyoFb, was induced by SD-208 despite maintained stress, shown by stress fiber de-polymerization in 30% of p-MyoFb vs in 8% of non-p-MyoFb. Stress fiber de-polymerization could be induced by mechanical strain release in p-MyoFb and non-p-MyoFb (2 day culture in unrestrained 3-D collagen matrices). Only p-MyoFb showed true dedifferentiation after long-term 3-D culture. Conclusions: Both reduction in mechanical strain and TGF--receptor-I kinase inhibition can reverse p-MyoFb differentiation but not in non-p-MyoFb.
Reversible and irreversible differentiation of cardiac fibroblasts.
Sex, Specimen part
View SamplesDisrupted differentiation is a hallmark of numerous diseases, which in epidermis alone impact >25% of the population. In a search for dominant mediators of differentiation, we defined a requirement for the ZNF750 nuclear protein in terminal epidermal differentiation. ZNF750 controlled genes mutated in numerous human skin diseases, including FLG, LOR, LCE3B, ALOXE3, and SPINK5. ZNF750 potently induced progenitor differentiation via an evolutionarily conserved C2H2 zinc finger motif. The epidermal master regulator, p63, bound the ZNF750 promoter and was necessary for its induction. ZNF750 restored differentiation to p63-deficient tissue, suggesting it acts downstream of p63. A search for functionally important ZNF750 targets via analysis of ZNF750-regulated genes identified KLF4, a transcription factor that activates late epidermal differentiation genes. ZNF750 binds the Klf4 promoter and controls its expression. ZNF750 thus provides a direct link between a tissue-specifying factor, p63, and an effector of terminal differentiation, Klf4, and represents a potential future target for disorders of this process.
ZNF750 is a p63 target gene that induces KLF4 to drive terminal epidermal differentiation.
Specimen part, Treatment
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