Addition of CO2 to the inspired gas can ameliorate lung injury during high tidal volume mechanical ventilation in animal models. Although some effects of hypercapnia on physiology and cell signaling have been characterized, we hypothesized that assessment of genome-wide gene expression patterns would reveal novel pathways of protection.
α-Tocopherol transfer protein mediates protective hypercapnia in murine ventilator-induced lung injury.
Sex, Specimen part
View SamplesHaving found that LexA degradation was significantly higher under apoptotic like death (ALD) than under SOS conditions, we hypothesized that additional genes tightly regulated by LexA would be transcribed under ALD conditions.
Apoptosis-like death, an extreme SOS response in Escherichia coli.
Disease, Treatment
View SamplesDespite education and aggressive treatment, breast cancer (BC) remains a clinical problem. BC cells (BCCs) can migrate early to metastatic sites where they may exist in cellular dormancy for decades. Presently, there are no consensus markers for cancer stem cells (CSCs) that are involved in tumor initiation and progression, and drug resistance. The current designation of CSCs might comprise similar tumor initiating cells, but at different developmental phase. In order to understand these differences, we developed a working hierarchy of BCCs. We initiated the studies in which three BCC subsets were selected based on the relative expressions of the stem cell-linked genes, Octamer4A (Oct4A). The sorted BCCs were subjected to array analyses using Affymetrix gene chip. Hierarchical clustering indicated distinct gene expression among the three subsets. Differential gene expressions of membrane proteins validated three novel genes, TMEM-98, GPR64 and FAT4. These three genes, in combination of known markers for CSCs, CD44, CD24, aldehyde dehydrogenase 1 (ALDH1) and Oct4A, were used to stratify BCCs led to a working hierarchy of BCCs. The validity of the hierarchical BCCs was applied to blood samples from patients, during relapse, and before and after treatment. These studies resulted in the patients grouped with distinct BCCs in the circulation. The relevance of the latter findings are discussed with regards to prediction of treatment response and time of BC relapse. The findings require a larger cohort of patients in a prospective multi-center study. The stratification could be important to understand treatment response, strategies for alternative approaches, and an understanding of the interaction between particular BCC subsets and the tissue microenvironment.
Evaluation of a developmental hierarchy for breast cancer cells to assess risk-based patient selection for targeted treatment.
Specimen part, Cell line
View SamplesStat1-null mice (129S6/SvEvTac-Stat1tm1Rds homozygous) uniquely develop estrogen-receptor-positive mammary tumors with incomplete penetrance and long latency. We studied the growth and development of the mammary glands in Stat1-null mice. Stat1-null MGs have faulty branching morphogenesis with abnormal terminal end buds. The Stat1-null MG also fails to sustain growth of 129S6/SvEv wild-type and null epithelium. These abnormalities are partially reversed by added progesterone and prolactin. Transplantation of wild-type bone-marrow into Stat1-null mice does not reverse the mammary gland developmental defects. Media conditioned by Stat1-null epithelium-cleared mammary fat pads does not stimulate epithelial proliferation whereas it is stimulated by conditioned media derived from either wild-type or progesterone and prolactin-treated Stat1-null epithelium-cleared mammary fat pads. Microarrays and multiplex cytokine protein assays showed that the mammary gland of Stat1-null mice had lower levels of growth factors that have been implicated in normal mammary gland growth and development. Transplanted Stat1-null tumors and their isolated cells also grow slower in Stat1-null mammary gland compared to wild-type recipient mammary gland. Stat1-null hosts responded to tumor transplants with granulocytic infiltrates while wild-type hosts show a mononuclear response. These studies demonstrate that growth of normal and neoplastic Stat1-null epithelium primarily depends on the hormonal milieu and factors, such as cytokines, from the mammary stroma.
Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent.
No sample metadata fields
View SamplesWe investigated at which stage of maturation commitment to a stable Foxp3-expressing phenotype takes place. We assessed stability of Foxp3 expression in thymic Foxp3+ Treg subsets of different maturity, defined by CD24 expression. Next we compared gene expression profiles of Foxp3+ Treg subsets (+) of different maturity (24lo, 24int, 24hi) and could identify a set of genes that were specifically up or downregulated in Foxp3+ Tregs, but not in Foxp3- conventional T cells, in a maturation-dependent manner.
Active demethylation of the Foxp3 locus leads to the generation of stable regulatory T cells within the thymus.
Specimen part
View SamplesPseudomonas aeruginosa is a common bacterium in the terminal plumbing system of buildings and it is from this niche that a substantial fraction of infections are acquired. To better understand P. aeruginosa biology in this environment, we examined the transcriptomes in tap water and pond water.
Transcriptional Responses of Pseudomonas aeruginosa to Potable Water and Freshwater.
No sample metadata fields
View SamplesIn contrast to urodele amphibians and teleost fish, mammals lack the regenerative responses to replace large body parts. Amphibian and fish regeneration uses dedifferentiation, i.e. reversal of differentiated state, as a means to produce progenitor cells to eventually replace damaged tissues. Therefore, activation of dedifferentiation response in mammalian tissues holds an immense promise for human regenerative medicine. msx2 expression has been shown to peak at the early time points of amphibian limb regeneration. Despite this temporal importance in the heterogenous regenerating limb tissues, the potential role of msx2 in dedifferentiation was previously not addressed in salamander or mammalian muscle cells. In order to test this, we ectopically overexpressed msx2 in mammalian myotubes and profiled their transcriptomes using next generation sequencing. We identified 4964 up-regulated and 4464 down-regulated transcripts in myotubes compared to myoblasts (uninduced GFP control cells; = 1.5 fold; FDR corrected p-values < 0.01). Upon ectopic msx2 expression in myotubes, 923 transcripts were downregulated, whereas 1283 transcripts were upregulated. Based on msx2's potential role in dedifferentiation, we reasoned that the transcripts, which are normally upregulated in myotubes in comparison to myoblasts, should go down upon msx2-expression. In accord with this idea, 575 myotube-enriched transcripts were downregulated after one day of ectopic msx2 expression. Similarly, 331 myoblast-enriched transcripts were upregulated upon msx2 expression. Overall design: To extensively analyze transcriptome-wide changes upon ectopic msx2 expression in mammalian myotubes, we performed next generation RNA-sequencing (RNA-seq) on uninduced and induced isolated myotubes that have msx2 and GFP or GFP alone transgenes. As a reference for the undifferentiated state, we also sequenced the transcriptomes of uninduced myoblast cultures of these two transgenic constructs. Deep sequencing was performed using Illumina HiSeq.
Ectopic expression of Msx2 in mammalian myotubes recapitulates aspects of amphibian muscle dedifferentiation.
No sample metadata fields
View SamplesInvestigation of global gene expression changes in Saccharomyces cerevisiae strain NRRL Y-12632 (ATCC 18824) grown in media made with asbestos mine tailings-laden water compared to the control grown in media made with double distilled water
Microarray data and gene expression statistics for <i>Saccharomyces cerevisiae</i> exposed to simulated asbestos mine drainage.
No sample metadata fields
View SamplesThis is an initial experiment which was performed in order to identify novel transcriptional targets of the tumor suppressor p53
p53 activates the PANK1/miRNA-107 gene leading to downregulation of CDK6 and p130 cell cycle proteins.
Specimen part, Cell line, Treatment
View SamplesRNA sequencing on LNCaP cells was carried out to study how tunicamycin-induced gene expression is affected by knockdown of EIF2AK3 and ATF4. Overall design: Samples from the below setup (treatments protocol) were harvested from four independent experiments. RNA integrity of total RNA samples was assessed by Bioanalyzer. All samples had RIN = 9.7.
The kinase PERK and the transcription factor ATF4 play distinct and essential roles in autophagy resulting from tunicamycin-induced ER stress.
Specimen part, Cell line, Treatment, Subject
View Samples