Project description:Purpose: Sox2 expression marks gastric stem and progenitor cells, raising important questions regarding the genes regulated by Sox2 and the role of Sox2 itself during stomach homeostasis and disease. The goal of this study is to determine the function of and the genes regulated by Sox2 in the stomach. Methods: Sox2 ChIP-enriched DNA and input DNA was isolated from gastric glands of adult antrum from Sox2 KO and Sox2 WT mice. DNA was purified and genomic libraries were prepared as described (Sulahian et al., 2014), using four micrograms of goat anti-SOX2 (AF2018, R&D). Libraries were sequenced (50 bp, single-end reads) on an Illumina Hi-Seq 2000 instrument. Results: Sox2 is dispensiable for gastric stem cell self-renewal and epithelial homeostasis, however modulates the expression of wnt, intestinal and cancer related genes Examination of Sox2 targets in the stomachs of Sox2 WT and Sox2 KO mice.
Project description:Purpose: Sox2 expression marks gastric stem and progenitor cells, raising important questions regarding the genes regulated by Sox2 and the role of Sox2 itself during stomach homeostasis and disease. The goal of this study is to determine the function of and the genes regulated by Sox2 in the stomach. Methods: mRNA profiles of Sox2 WT and Sox2 KO gastric glands were generated by RNA-sequencing, in triplicate, using a Illumina HiSeq 2500 instrument, resulting in 36 million single-end 50bp reads per smaple. Sequencing reads were mapped to the mouse reference genome (mm10/GRCm38) using STAR (Dobin et al., 2013). Read counts over transcripts were calculated using HTSeq v.0.6.0 (Anders et al., 2015) based on a current Ensembl annotation file for mm10/GRCm38 (release 75). Results: Sox2 is dispensiable for gastric stem cell self-renewal and epithelial homeostasis, however modulates the expression of cancer and intestinal related genes. mRNA profiles of stomachs from 10 week old Sox2 WT and Sox2 KO mice were generated by sequencing, in triplicate, using a Illumina HiSeq 2500.
Project description:Purpose: Sox2 expression marks gastric stem and progenitor cells, raising important questions regarding the genes regulated by Sox2 and the role of Sox2 itself during stomach homeostasis and disease. The goal of this study is to determine the function of and the genes regulated by Sox2 in the stomach. Methods: Sox2 ChIP-enriched DNA and input DNA was isolated from gastric glands of adult antrum from Sox2 KO and Sox2 WT mice. DNA was purified and genomic libraries were prepared as described (Sulahian et al., 2014), using four micrograms of goat anti-SOX2 (AF2018, R&D). Libraries were sequenced (50 bp, single-end reads) on an Illumina Hi-Seq 2000 instrument. Results: Sox2 is dispensiable for gastric stem cell self-renewal and epithelial homeostasis, however modulates the expression of wnt, intestinal and cancer related genes
Project description:Purpose: Sox2 expression marks gastric stem and progenitor cells, raising important questions regarding the genes regulated by Sox2 and the role of Sox2 itself during stomach homeostasis and disease. The goal of this study is to determine the function of and the genes regulated by Sox2 in the stomach. Methods: mRNA profiles of Sox2 WT and Sox2 KO gastric glands were generated by RNA-sequencing, in triplicate, using a Illumina HiSeq 2500 instrument, resulting in 36 million single-end 50bp reads per smaple. Sequencing reads were mapped to the mouse reference genome (mm10/GRCm38) using STAR (Dobin et al., 2013). Read counts over transcripts were calculated using HTSeq v.0.6.0 (Anders et al., 2015) based on a current Ensembl annotation file for mm10/GRCm38 (release 75). Results: Sox2 is dispensiable for gastric stem cell self-renewal and epithelial homeostasis, however modulates the expression of cancer and intestinal related genes.
Project description:Gastric cancer is still one of the most common causes of cancer-related death worldwide, which is mainly attributable to late diagnosis and poor treatment options. Infection with H. pylori, different environmental factors and genetic alterations are known to influence the risk of developing gastric tumors. However, the molecular mechanisms involved in gastric carcinogenesis are still not fully understood, making it difficult to design targeted therapeutic approaches. Aberrant expression of the specific gastric differentiation marker Sox2 (sry-related HMG box 2) has been observed in stomach cancer. However, the role of Sox2 in gastric tumors has not been well established to date. To elucidate the role of Sox2 in gastric tumorigenesis, Sox2 transcriptional activity was blocked in AZ521 cells. Interestingly, inhibition of Sox2 reduced cell proliferation and migration, increased apoptosis and induced changes in cell cycle. Blocking of Sox2 also reduced the tumorigenic potential of AZ521 cells in vivo. In addition, correlation of Sox2 expression and proliferation was observed in a subset of human gastric tumours. Finally, target genes of Sox2 were for the first time identified by RNA microarray in gastric cancer cells. Taken together, the results presented here indicate that Sox2 controls several aspects related to gastric cancer development and progression by regulating the expression of members of important signalling pathways. These findings could provide new therapeutic options for a subset of gastric cancers exhibiting Sox2 deregulation. Inducible dnSox2 in AZ521 cells, 4 timepoints with/without induction.
Project description:Gastric cancer is still one of the most common causes of cancer-related death worldwide, which is mainly attributable to late diagnosis and poor treatment options. Infection with H. pylori, different environmental factors and genetic alterations are known to influence the risk of developing gastric tumors. However, the molecular mechanisms involved in gastric carcinogenesis are still not fully understood, making it difficult to design targeted therapeutic approaches. Aberrant expression of the specific gastric differentiation marker Sox2 (sry-related HMG box 2) has been observed in stomach cancer. However, the role of Sox2 in gastric tumors has not been well established to date. To elucidate the role of Sox2 in gastric tumorigenesis, Sox2 transcriptional activity was blocked in AZ521 cells. Interestingly, inhibition of Sox2 reduced cell proliferation and migration, increased apoptosis and induced changes in cell cycle. Blocking of Sox2 also reduced the tumorigenic potential of AZ521 cells in vivo. In addition, correlation of Sox2 expression and proliferation was observed in a subset of human gastric tumours. Finally, target genes of Sox2 were for the first time identified by RNA microarray in gastric cancer cells. Taken together, the results presented here indicate that Sox2 controls several aspects related to gastric cancer development and progression by regulating the expression of members of important signalling pathways. These findings could provide new therapeutic options for a subset of gastric cancers exhibiting Sox2 deregulation.