During the peri-partum period, the lung must respond to many factors with potential to impact protein synthesis via regulation of translation initiation. Microarray analysis of polysomal versus total RNA from fetal day (FD) 19, FD22 and postnatal day 1 (P1) rat lungs was used to identify genes whose association with large polysomes changed either pre- or postnatally.
Global and gene-specific translational regulation in rat lung development.
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View SamplesNormal adult liver is uniquely capable of renewal
Restoration of liver mass after injury requires proliferative and not embryonic transcriptional patterns.
Age
View SamplesPURPOSE:
Unique gene expression profile based on pathologic response in epithelial ovarian cancer.
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View SamplesAddition 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 SamplesMind-body practices that elicit the relaxation response (RR) have been used worldwide for millennia to prevent and treat disease. The RR is believed to be the counterpart to stress response and is characterized by decreased oxygen consumption, increased exhaled nitric oxide, and reduced psychological distress. Individuals experiencing chronic psychological stress have the opposite pattern of physiology and a characteristic transcriptional profile. We hypothesized that consistent, long-term practice of RR techniques results in characteristic changes in gene expression. We tested this hypothesis by assessing the transcriptional profile of whole blood in healthy, long-term practitioners of daily RR practice (group M) in comparison to healthy controls (group N1). The signature obtained has been validated on new subject data.
Genomic counter-stress changes induced by the relaxation response.
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View SamplesIn order to address the progression, metastasis, and clinical heterogeneity of renal cell cancer (RCC), transcriptional profiling with oligonucleotide microarrays (22,283 genes) was done on 49 RCC tumors, 20 non-RCC renal tumors, and 23 normal kidney samples. Samples were clustered based on gene expression profiles and specific gene sets for each renal tumor type were identified. Gene expression was correlated to disease progression and a metastasis gene signature was derived. Gene signatures were identified for each tumor type with 100% accuracy. Differentially expressed genes during early tumor formation and tumor progression to metastatic RCC were found. Subsets of these genes code for secreted proteins and membrane receptors and are both potential therapeutic or diagnostic targets. A gene pattern ("metastatic signature") derived from primary tumors was very accurate in classifying tumors with and without metastases at the time of surgery. A previously described "global" metastatic signature derived by another group from various non-RCC tumors was validated in RCC. Unlike previous studies, we describe highly accurate and externally validated gene signatures for RCC subtypes and other renal tumors. Interestingly, the gene expression of primary tumors provides us information about the metastatic status in the respective patients and has the potential, if prospectively validated, to enrich the armamentarium of diagnostic tests in RCC. We validated in RCC, for the first time, a previously described metastatic signature and further showed the feasibility of applying a gene signature across different microarray platforms. Transcriptional profiling allows a better appreciation of the molecular and clinical heterogeneity in RCC.
Gene signatures of progression and metastasis in renal cell cancer.
Specimen part
View SamplesThe identification of genes and deduced pathways from the mature human oocyte can help us better understand oogenesis, folliculogenesis, fertilization, and embryonic development. Human metaphase II oocytes were used within minutes after removal from the ovary, and its transcriptome was compared with a reference sample consisting of a mixture of total RNA from 10 different normal human tissues not including the ovary. RNA amplification was performed by using a unique protocol. Affymetrix Human Genome U133 Plus 2.0 GeneChip arrays were used for hybridizations. Compared with reference samples, there were 5,331 transcripts significantly up-regulated and 7,074 transcripts significantly down-regulated in the oocyte. Of the oocyte up-regulated probe sets, 1,430 have unknown function. A core group of 66 transcripts was identified by intersecting significantly up-regulated genes of the human oocyte with those from the mouse oocyte and from human and mouse embryonic stem cells. GeneChip array results were validated using RT-PCR in a selected set of oocyte-specific genes. Within the up-regulated probe sets, the top overrepresented categories were related to RNA and protein metabolism, followed by DNA metabolism and chromatin modification. This report provides a comprehensive expression baseline of genes expressed in in vivo matured human oocytes. Further understanding of the biological role of these genes may expand our knowledge on meiotic cell cycle, fertilization, chromatin remodeling, lineage commitment, pluripotency, tissue regeneration, and morphogenesis.
The transcriptome of human oocytes.
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View SamplesHuman Notch1 intracellular domain (NICD) was overexpressed in human primary lymphatic endothelial cells (LECs) for 10 and 24 hours by adenovirus. A GFP-control adenovirus-infected cells (24hours) and uninfected cells were also analysed as controls.
An exquisite cross-control mechanism among endothelial cell fate regulators directs the plasticity and heterogeneity of lymphatic endothelial cells.
Specimen part
View SamplesKnockdown of the transcription factor PU.1 (Spi1) leads to acute myeloid leukemia (AML) in mice. We examined the transcriptome of PU.1 knockdown hematopoietic stem cells (HSC) in the preleukemic phase by linear amplification and genome-wide array analysis to identify transcriptional changes preceding malignant transformation. Hierarchical cluster analysis and principal component analysis clearly distinguished PU.1 knockdown from wildtype HSC. Jun family transcription factors c-Jun and JunB were among the top downregulated targets. Retroviral restoration of c-Jun expression in bone marrow cells of preleukemic mice partially rescued the PU.1-initiated myelomonocytic differentiation block. Lentiviral restoration of JunB at the leukemic stage led to reduced clonogenic growth, loss of leukemic self-renewal capacity, and prevented leukemia in transplanted NOD-SCID mice. Examination of 305 AML patients confirmed the correlation between PU.1 and JunB downregulation and suggests its relevance in human disease. These results delineate a transcriptional pattern that precedes the leukemic transformation in PU.1 knockdown HSC and demonstrate that decreased levels of c-Jun and JunB contribute to the development of PU.1-induced AML by blocking differentiation (c-Jun) and increasing self-renewal (JunB). Therefore, examination of disturbed gene expression in HSC can identify genes whose dysregulation is essential for leukemic stem cell function and are targets for therapeutic interventions.
Essential role of Jun family transcription factors in PU.1 knockdown-induced leukemic stem cells.
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