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GSE47772
Mus musculus
24 Downloadable Samples
Description
Constitutive activation of the Wnt pathway leads to adenoma formation, an obligatory step towards intestinal cancer. In view of the established role of Wnt in regulating stemness, we attempted the isolation of cancer stem cells (CSCs) from Apc- and Apc/KRAS-mutant intestinal tumours. Whereas CSCs are present in malignant Apc/KRASmutant carcinomas, they appear to be very rare (<10-6) in the benign Apcmutant adenomas. In contrast, the Lin-CD24hiCD29+ subpopulation of adenocarcinoma cells appear to be enriched in CSCs with increased levels of active -catenin. Expression profiling analysis of the CSC-enriched subpopulation confirmed their enhanced Wnt activity and revealed additional differential expression of other signalling pathways, growth factor binding proteins, and extracellular matrix components. As expected, genes characteristic of the Paneth cell lineage (e.g. defensins) are co-expressed together with stem cell genes (e.g. Lgr5) within the CSC-enriched subpopulation. This is of interest as it may indicate a cancer stem cell niche role for tumor-derived Paneth-like cells, similar to their role in supporting Lgr5+ stem cells in the normal intestinal crypt. Overall, our results indicate that oncogenic KRAS activation in Apc-driven tumours results in the expansion of the CSCs compartment by increasing b-catenin intracellular stabilization.
Publication Title
Cancer stemness in Apc- vs. Apc/KRAS-driven intestinal tumorigenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
NRASG12V oncogene facilitates self-renewal in a murine model of acute myelogenous leukemia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 54 Downloadable Samples
Description
The Melanoma-associated Antigen gene family (MAGE) generally encodes for tumour antigens. We recently have identified one of the MAGE gene members, Mageb16 to be highly expressed in undifferentiated murine embryonic stem cells (mESCs). The role of Mageb16 for the differentiation of the pluripotent stem cells is completely unknown. Here we demonstrate that Mageb16 (41 kDa) is distributed in cytosol and/or in surface membrane in undifferentiated mESCs. A transcriptome study was performed with differentiated short hairpin RNA (shRNA)-mediated Mageb16 knockdown (KD ESCs) and scrambled control (SCR) ESCs until a period of 22 days. Mageb16 KD ESCs mainly differentiated towards mesodermal derivatives such as cardiovascular lineages. Mesoderm-oriented differentiation initiated biological processes such as adipogenesis, osteogenesis, limb morphogenesis and spermatogenesis were significantly enriched in the differentiated Mageb16 KD ESCs. Cardiomyogenesis in differentiated KD mESCs was stronger when compared to differentiated SCR and wild mESCs. The expression of non-coding RNA (ncRNA) Lin28a and other epigenetic regulatory genes, nucleocytoplasmic trafficking and genes participating in spermatogenesis have also declined faster in the differentiating Mageb16 KD ESCs. We conclude that Mageb16 plays a crucial role for differentiation of ESCs, specifically to the mesodermal lineages. Regulative epigenetic networks and nucleocytoplasmic modifications induced by Mageb16 may play a role for the critical role of Mageb16 for the ESCs differentiation.
Publication Title
Depletion of Mageb16 induces differentiation of pluripotent stem cells predominantly into mesodermal derivatives.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 17 Downloadable Samples
Description
Various substances have been reported to enhance the cardiac differentiation of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Ascorbic Acid had a cardiogenic effect in mESC CGR8 cell line. Transcriptome of AA-treated CGR8 ESCs did not reveal any significant changes in gene expression as compared to untreated cells.
Publication Title
Ascorbic Acid-Induced Cardiac Differentiation of Murine Pluripotent Stem Cells: Transcriptional Profiling and Effect of a Small Molecule Synergist of Wnt/β-Catenin Signaling Pathway.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 17 Downloadable Samples
Description
Tumor growth is associated with a profound alteration of myelopoiesis, leading to recruitment of immunosuppressive cells known as myeloid-derived suppressor cells (MDSCs). Immuno-regulatory activity of both tumor-induced and BM-derived MDSCs (by GM-CSF and IL-6 treatment) was entirely dependent on C/EBP transcription factor (TF), a key component of the emergency myelopoiesis triggered by stress and inflammation. We used miR expression analysis to identify miRs which could drive MDSC recruitment/generation/activity by modulating specific TFs and pathway. In particular, we identified a miR signature of 79 miR differentially expressed between not suppressive CD11b+ cells and CD11b+ isolated from tumor mass and spleen of tumor-bearing mice. Moreover on the same samples we profiled gene expression with Affymetrix microarrays to perform an integrated analysis of mirna and gene expression.
Publication Title
miR-142-3p prevents macrophage differentiation during cancer-induced myelopoiesis.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Cell line
View Samples