Puberty unmasks or accelerates nephropathies, including the nephropathy of diabetes mellitus (DM). A number of cellular systems implicated in the kidney disease of DM interweave, forming an interdependent functional web. We performed focused microarray analysis to test the hypothesis that one or more genes in the transforming growth factor beta (TGF-) signaling system would be differentially regulated in male rats depending on the age of onset of DM.
Prepubertal onset of diabetes prevents expression of renal cortical connective tissue growth factor.
No sample metadata fields
View SamplesC3H10T1/2 stem cells are committed to the adipocyte lineage by treatment with BMP-4 and grown to postconfluence. When subjected to our standard differentiation protocol, the committed cells differentiate into adipocytes in a manner indistinguishable from that of 3T3-L1 preadipocytes. In contrast, C3H10T1/2 cells not committed with BMP-4 remain undifferentiated despite treatment with differentiation inducers. The molecular basis of the commitment process, however, has not been elucidated. Since postconfluent uncommitted and committed C3H10T1/2 cells respond differently to the differentiation inducers, it was reasoned that the two cell types differed at the gene expression level. Therefore, we undertook microarray gene expression profiling to detect changes between the two cell populations at postconfluence to identify expressed genes that may be responsible for the dramatic change in phenotype.
BMP-4 treatment of C3H10T1/2 stem cells blocks expression of MMP-3 and MMP-13.
No sample metadata fields
View SamplesE2 exposure significantly decreased peak viral titer in hNECs from female donors. We used microarray analyses to identify global gene expression patterns between E2 and vehicle exposed hNECs from female donors
Estrogenic compounds reduce influenza A virus replication in primary human nasal epithelial cells derived from female, but not male, donors.
Sex, Specimen part, Treatment
View SamplesPrevious studies in our laboratory demonstrated that the azurophil granule protease neutrophil elastase (NE) cleaves PML-RARA (PR), the fusion protein that initiates acute promyelocytic leukemia (APL). Further, NE deficiency reduces the penetrance of APL in a murine model of this disease. We therefore predicted that NE-mediated PR cleavage might be important for its ability to initiate APL. To test this hypothesis, we generated a mouse expressing NE-resistant PR. These mice developed APL indistinguishable from wild type PR, but with significantly reduced latency (median leukemia-free survival of 274 days versus 473 days for wild type PR, p<0.001). Resistance to proteolysis may increase the abundance of full length PR protein in early myeloid cells, and our previous data suggested that non-cleaved PR may be less toxic to early myeloid cells. Together, these effects appear to increase the leukemogenicity of NE-resistant PR, contrary to our previous prediction. We conclude that NE deficiency may reduce APL penetrance via indirect mechanisms that are still NE dependent.
A protease-resistant PML-RAR{alpha} has increased leukemogenic potential in a murine model of acute promyelocytic leukemia.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Autophagy maintains the metabolism and function of young and old stem cells.
Specimen part
View SamplesMicroarray-based gene expression data were generated from RNA from Ls174T colorectal carcinoma cell lines in which Wnt-dependent transcriptional activity can be abrogated by inducible overexpression of a dominant-negative form of Tcf4 or siRNA against -catenin.
Integrated genome-wide analysis of transcription factor occupancy, RNA polymerase II binding and steady-state RNA levels identify differentially regulated functional gene classes.
Specimen part, Cell line, Time
View SamplesAutophagy is critical for protecting HSCs from metabolic stress. Here, we used a genetic approach to inactivate autophagy in adult HSCs by deleting the Atg12 gene. We show that loss of autophagy causes accumulation of mitochondria and an oxidative phosphorylation (OXPHOS)-activated metabolic state, which drives accelerated myeloid differentiation likely through epigenetic deregulations rather than transcriptional changes, and impairs HSC self-renewal activity and regenerative potential.
Autophagy maintains the metabolism and function of young and old stem cells.
Specimen part
View SamplesParathyroid hormone (PTH) and PTH-related protein (PTHrP) are involved in cachexia associated with chronic kidney disease and cancer respectively. Tumor-derived PTHrP triggers adipose tissue browning and thereby leads to wasting of fat tissue in tumor-bearing mice. Similarly, elevated in 5/6 nephrectomized mice, PTH stimulates adipose tissue browning and wasting. Mice lacking the PTH/PTHrP receptor in their fat tissue are resistant to wasting of both adipose tissue and skeletal muscle. Therefore, the PTH/PTHrP signaling in adipocytes should activate various pathways that contribute to hypermetabolism and muscle wasting.
PTH/PTHrP Receptor Mediates Cachexia in Models of Kidney Failure and Cancer.
Sex, Specimen part
View SamplesECRG4 is a promising tumor suppressor gene (TSG) recently identified in esophageal carcinoma. Its expression and prognostic value have never been explored in breast cancer. Using DNA microarray, we examined ECRG4 mRNA expression in 353 invasive breast cancer samples. A meta-analysis was performed on a large public retrospective gene expression dataset (n=1,387) to analyze correlation between ECRG4 expression and histo-clinical features including survival.
Down-regulation of ECRG4, a candidate tumor suppressor gene, in human breast cancer.
Age, Specimen part
View SamplesEven though T-cell receptor (TCR) stimulation together with co-stimulation is sufficient for the activation of both na誰ve and memory T cells, the memory cells are capable of producing lineage specific cytokines much more rapidly than the na誰ve cells. The mechanisms behind this rapid recall response of the memory cells are still not completely understood. Here, we performed epigenetic profiling of human resting na誰ve, central and effector memory T cells using ChIP-Seq and found that unlike the na誰ve cells, the regulatory elements of the cytokine genes in the memory T cells are marked by activating histone modifications even in the resting state. Therefore, the ability to induce expression of rapid recall genes upon activation is associated with the deposition of positive histone modifications during memory T cell differentiation. We propose a model of T cell memory, in which immunological memory state is encoded epigenetically, through poising and transcriptional memory. Overall design: Chromatin state of resting Human Naive, Central memory (TCM) and Effector Memory (TEM) T cells was analyzed by ChIP-Seq; Gene expression in resting and activated for 40 min, 150 min and 15hrs Naive, TCM and TEM cells was analyzed by RNA-Seq
Rapid Recall Ability of Memory T cells is Encoded in their Epigenome.
No sample metadata fields
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