Dysferlin is expressed in skeletal and cardiac muscle. However, dysferlin deficiency, namely limb girdle muscular dystrophy 2B (LGMD2B) and Myoshi myopathy, results in skeletal muscle weakness and spares the heart. This dichotomy could be caused by differential regulation of protective mechanisms. Therefore, we compared intraindividual mRNA expression profiles between cardiac and skeletal muscle in dysferlin-deficient SJL/J mice and normal C57BL/6 mice.
No associated publication
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Primate-specific endogenous retrovirus-driven transcription defines naive-like stem cells.
Sex, Specimen part, Cell line
View SamplesWe surveyed RNA-Seq data to identify those TEs that are transcriptionally active uniquely in human pluripotent cells. We identified one endogenous retrovirus (HERV-H) family, uniquely found in primates as being unusually abundant in the transcriptome. The microarray data provided is to support our human naive cell hypothesis.
Primate-specific endogenous retrovirus-driven transcription defines naive-like stem cells.
Sex, Cell line
View SamplesThe combined activation of Wnt/-catenin and MET/HGF is required for mammary cancer stem cell (MaCSC) maintenance. We generated mammospheres derived from tumors of mice harboring Wnt/Met signaling mutations on which we performed microarray analysis to evaluate gene expression signatures controlled by Wnt and MET pathways. We used the gene expression profiles to dissect the role and the functions of these pathways in MaCSCs.
Combined Wnt/β-catenin, Met, and CXCL12/CXCR4 signals characterize basal breast cancer and predict disease outcome.
Specimen part, Treatment
View SamplesAnalysis of hematopoietic stem cells (HSC, LSK Flt3-) and myeloid progenitors (MP, LK CD34+) sorted from wildtype and Dnmt1 hypomorph mice
DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction.
Specimen part
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Loss of the Hematopoietic Stem Cell Factor GATA2 in the Osteogenic Lineage Impairs Trabecularization and Mechanical Strength of Bone.
Cell line
View SamplesThe endocytic receptor megalin constitutes the main pathway for clearance of plasma proteins from the glomerular filtrate in the proximal tubules. However, little is know about the mechanisms that control receptor activity. A widely discussed hypothesis states that the intracellular domain (ICD) of megalin, released upon ligand binding, acts as a transcription regulator to suppress receptor expression - a mechanism proposed to safeguard the proximal tubules from protein overload. Here, we have put this hypothesis to the test by generating a mouse model co-expressing the soluble ICD and the full-length receptor. Despite pronounced expression in the proximal tubules, the ICD failed to exert any effects on renal proximal tubular function such as megalin expression, protein retrieval, or renal gene transcription. Thus, our data argue that the ICD does not play a role in regulation of megalin activity in vivo in the proximal tubules.
The soluble intracellular domain of megalin does not affect renal proximal tubular function in vivo.
Sex, Age, Specimen part
View SamplesGATA2 is a transcription factor that is required for hematopoietic stem cell (HSC) differentiation. GATA2 is also expressed in mesenchymal cells and blocks differentiation of both white and brown adipocytes by interfering with C/EBP activity and PPAR expression. By studying genome-wide binding sites of endogenous GATA2 in mesenchymal stem cells (MSC), we discovered a previously unrecognized function of GATA2 in the regulation of skeletal development-related genes. In contrast to hematopoietic stem cells, canonical GATA2 binding motifs in MSCs co-localized with motifs for transcription factors of the FOX and HOX family, known regulators of skeletal development. Consistently, ectopic GATA2 expression in MSCs regulated many osteoblast-related genes. Ectopic GATA2 blocked, whereas GATA2 deletion enhanced differentiation of osteoblastic precursors. GATA2 expression inhibited bone morphogenetic protein (BMP)-2 induced SMAD1/5/8 activity, a pathway that drives osteoblastogenesis. MSC-specific deletion of GATA2 in mice affected both numbers and osteogenic potential of bone-residing precursors without disturbing normal skeletal development. In adult mice, MSC-specific GATA2 deficiency affected trabecular bone structure and its mechanical properties. blood phenotype? In summary, our study identified GATA2 as a novel regulator of osteoblast differentiation and bone morphology, suggesting a role of GATA2 in MSC lineage determination that goes beyond adipocyte differentiation.
Loss of the hematopoietic stem cell factor GATA2 in the osteogenic lineage impairs trabecularization and mechanical strength of bone.
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View SamplesMicroRNAs (miRNAs) have emerged as important gene regulators and are recognized as key players in tumorigenesis. miR-143 is reported to be down-regulated in several cancers, but knowledge of its targets in colon cancer remains limited. To investigate the role of miR-143 in colon cancer, we have employed a microarray based approach to identify miR-143 targets. Based on seed site enrichment analyses and unbiased word analyses, we found a significant enrichment of miRNA binding sites in the 3-untranslated regions (UTRs) of transcripts down-regulated upon miRNA overexpression. Here we identify Hexokinase 2 (HK2) as a direct target of miR-143 and show that re-introduction of miR-143 in the colon cancer cell line DLD-1 results in a decreased lactate secretion, indicating that miR-143 down-regulation of HK2 affects glucose metabolism in colon cancer cells.
No associated publication
Specimen part, Cell line
View SamplesAn Hodgkin Lymphoma cell line have been treated with an LNA inhibitor for miR-9 or with a scramble LNA to identify miR-9 regulated pathways that could be important for Hodgkin Lymphoma pathogenesis.
Inhibition of miR-9 de-represses HuR and DICER1 and impairs Hodgkin lymphoma tumour outgrowth in vivo.
Cell line, Treatment
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