Skeletal muscle must perform a wide range of kinds of work, and different fiber types have evolved to accommodate these different tasks. The attributes of fibers are determined in large part by the coordinated regulation of oxidative capacity, as reflected by mitochondrial content, and the specific makeup of myofibrillar proteins. Adult muscle fibers contain four myosin heavy chain isotypes: I, IIa, IIx and IIb. Type I and IIa fibers have slower twitches and are rich in mitochondria, while type IIb fibers are fast-twitch and predominantly glycolytic. The intermediate IIx fibers are less well understood. Previous work had shown that the transcriptional coactivator PGC-1 alpha could drive the formation of type I and IIa muscle fibers. We show here that mice with transgenic expression of PGC-1 beta in skeletal muscle results in marked induction of IIx fibers. The fibers in transgenic mice are rich in mitochondria and are highly oxidative. As a result, PGC-1 beta transgenic animals can perform oxidative activity for longer and at higher work loads than wild type animals. In cell culture, PGC-1 beta coactivates the MEF2 family of transcription factors to stimulate the MHC IIx promoter. Together, these data indicate that PGC-1 beta is sufficient to drive the formation in vivo of highly oxidative fibers with type IIx characteristics.
The transcriptional coactivator PGC-1beta drives the formation of oxidative type IIX fibers in skeletal muscle.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
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View SamplesHGSOC, the most aggressive form of OC, is characterized by insidious onset, rapid intraperitoneal spread and development of massive ascites. Peritoneal adhesion was considered as the first step of abdominal metastasis, underscoring that only tumor cells gain access to peritoneal adherence contribute to metastasis. Studies on ovarian cancer progression were mainly focused on the primary and metastatic tumor cells, while understanding of the ascitic tumor cells is limited. We hypothesized that uncovering the gene expression profiles of ascitic tumor cells from high grade serous ovarian cancer patients will allow us to understand more specifically their unique phenotype which mediates the peritoneal adhesion. In this study, gene expression profiling was completed for 15 magnetic sorted tumor cells samples from matched primary tumors, ascites and metastases of 5 high grade serous ovarian cancer patients. By comparing the expression data from ascitic tumor cells with primary and metastasis tumor cells, we identified a set of differential expressed genes in ovarian ascitic tumor cells advantageous for peritoneal adhesion and metastasis. Further study revealed that ascites microenvironment modulated the ascitic tumor cells phenotype and contributed to ovarian cancer dissemination through facilitating CAFs in formation of compact spheroids with ascitic tumor cells.
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View SamplesDiffer from the aggressive nature of HGSOC (high grade serous ovarian cancer), LGSOC (low grade serous ovarian cancer) is characterized by an early age of disease onset, slow growth pattern, and poor response to chemotherapy. To understand more specifically the underlying gene profiling discrepancy that contributes to their behavior distinction, we performed parallel gene expression profiling in 9 magnetic sorted tumor cells samples from matched primary tumors, ascites and metastases of 3 LGSOC patients as in HGSOC. By comparing the expression data among primary tumor cells, ascitic tumor cells and metastasis tumor cells, we identified a set of differential expressed genes along LGSOC progression. Further study revealed that the gene phenotype perturbance along LGSOC progression was quite different from that of HGSOC patients.
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View SamplesInteraction between stromal cells and the tumor greatly influences tumor initiation and progression. Cancer-associated fibroblasts (CAFs) are the major component of tumor stroma and play a key role in ovarian cancer (OC) cells adhesion and metastasis. CAFs were found abundantly in primary tumor and metastases, as well as in malignant ascites of high grade serous OC patients, underscoring that CAFs modulate OC cells phenotype and facilitate disease exacerbation along OC progression. Studies of CAFs exertion on OC mainly focused on the influence of CAFs conditioned medium (CM) influence of tumor cells phenotype, while ignoring the fact that CAFs are supposed to be in intimate contact with neoplastic cells in tumor mass, and that CAFs also form compact heterotypic spheroids with ascitic tumor cells in malignant ascites. We hypothesized that uncovering the underlying molecules that mediate tumor cells binding with CAFs could aid in developing measures destroying the pro-carcinogenic heterotypic spheroids in malignant ascites. In this study, gene expression profiling was completed for individual SKOV3, and magnetic sorted SKOV3 cells that form heterotypic spheroids with 4 cases of high grade serous OC derived CAFs. By comparing the expression data of SKOV3 cells in individual group with that in spheroid group, we identified a set of differential expressed genes. This study revealed the heterogeneity of ascitic tumor cells and raised potent therapeutical targets in destroying of the heterotypic spheroids in malignant ascites of OC.
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Specimen part, Cell line
View SamplesOvarian cancer (OC) remains the leading cause of death in patients with gynecological malignancy. An improved understanding of the genomics has led to the separation of OC into histologically and molecularly defined subgroups. Based on molecular profiling in OC patients, subtype with a reactivated tumor stroma presented the worst prognosis, emphasizing the importance of tumor microenvironment especially stromal fibroblasts in fueling OC progression. Dicer1 is well recognized as the microRNA (miR) synthesis machinery, playing a crucial role in cellular maturation and development, and was generally considered to be a tumor suppressor gene that inhibited tumor initiation and metastasis. Dicer1 expression pattern and exact biological function was seldom studied in the stromal compartment. There was a recent study demonstrating that Dicer1 was involved in mouse embryonic fibroblast (MEF) development and maturation. Therefore, we are inspired to explore the expression and function of Dicer1 in stromal fibroblasts of OC patients. In this study, mRNA and microRNA gene expression profiling were conducted for MRC5-CAFs after silencing of Dicer1. By comparing the expression data of MRC5-CAFs transfected with control siRNA (si-Ctrl) or with Dicer1 specific siRNA (si-Dicer1) for 72 hr, we identified a set of differential expressed mRNA and microRNA in MRC5-CAFs after Dicer1 knockdown. This study was the first to investigate Dicer1 influence of stromal fibroblast gene expression and the underlying regulation mechanism, which held great importance in complementing our understanding of Dicer1 in OC initiation and development, and raises potent therapeutical targets in controlling OC metastasis
Dicer reprograms stromal fibroblasts to a pro-inflammatory and tumor-promoting phenotype in ovarian cancer.
Specimen part
View SamplesMicroarray analysis of parity induced gene expression changes in the mammary glands of four strains of rats to identify a common gene signature associated with protection against methylnitrosourea induced mammary tumorigenesis.
Hormone-induced protection against mammary tumorigenesis is conserved in multiple rat strains and identifies a core gene expression signature induced by pregnancy.
Age, Specimen part
View SamplesAML patient samples and a few normal blood sample were assayed for H3K27ac ChIP-seq and RNA-seq. We discovered subtypes of AML based on these enhancer landscapes.
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View SamplesLITE-Seq 3'' end capture and sequencing of the C. elegans germline
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Sex, Specimen part, Cell line
View SamplesThis microarray experiment serves to identify the genes in the Arabidopsis genome that are regulated by carbon and light signaling interactions in 7 day dark grown seedlings. The expression profile of wild-type will be compared to the cli186 mutant, a mutant defective in carbon and light signaling. Plants of both the wild-type and cli186 genotypes are treated with the following light (L) and carbon (C) treatments: -C-L, +C-L, +C+L, -C+L. Comparison of the expression profiles under all treatments will help to identify genes that are misregulated in carbon and/or light treatments in the cli186 mutant.
An integrated genetic, genomic and systems approach defines gene networks regulated by the interaction of light and carbon signaling pathways in Arabidopsis.
Age
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