Attractor landscape analysis reveals a reversion switch in the transition of colorectal tumorigenesis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE283167 | GEO | 2025/02/12
REPOSITORIES: GEO
Similar Datasets
Project description:Liver fibrosis is characterized by the excessive formation and accumulation of matrix proteins as a result of wound healing in the liver. A main event during fibrogenesis is the activation of the liver resident quiescent hepatic stellate cell (qHSC). Recent studies suggest that reversion of the activated HSC (aHSC) phenotype into a quiescent-like phenotype could be a major cellular mechanism underlying fibrosis regression in the liver, thereby offering new therapeutic perspectives for the treatment of liver fibrosis. The goal of the present study is to identify experimental conditions that can revert the activated status of human HSCs and to map the molecular events associated with this phenotype reversion by gene expression profiling Transcriptomic profiling of primary human quiescent HSCs (qHSCs), in vitro activated HSCs (aHSCs) and in vitro reverted HSCs (rHSCs). The cell types come from different donors (This is detailed in the original manuscript.).
2015-08-12 | E-GEOD-68001 | biostudies-arrayexpress
Project description:Liver fibrosis is characterized by the excessive formation and accumulation of matrix proteins as a result of wound healing in the liver. A main event during fibrogenesis is the activation of the liver resident quiescent hepatic stellate cell (qHSC). Recent studies suggest that reversion of the activated HSC (aHSC) phenotype into a quiescent-like phenotype could be a major cellular mechanism underlying fibrosis regression in the liver, thereby offering new therapeutic perspectives for the treatment of liver fibrosis. The goal of the present study is to identify experimental conditions that can revert the activated status of human HSCs and to map the molecular events associated with this phenotype reversion by gene expression profiling
2015-08-12 | GSE68001 | GEO
Project description:Attractor landscape analysis reveals a reversion switch in the transition of colorectal tumorigenesis
| PRJNA1192268 | ENA
Project description:Suppressor of cytokine signaling (SOCS1) is an inducible negative regulator of cytokine signaling. SOCS1 is expressed in normal colonic epithelium and colon adenocarcinomas. However, the levels of SOCS1 decreased during progression of colon adenocarcinomas, the lowest level being found in the more aggressive stage and least differentiated carcinomas. The restoration of SOCS1 in a colon cancer cell line induced expression of E-cadherin associated with disappearance of the mesenchymal form of the p120ctn. SOCS1 expression is sufficient to revert many characteristics of EMT. This reversion is dependent on the regulation of expression of the transcription factor ZEB1, both at transcriptional and translational levels. Furthermore, miRNA profiling indicates that SOCS1 also upregulates the expression of the mir-200 family of microRNAs, which can promote the mesenchymal-epithelial transition and reduce tumor cell migration. Expression of SOCS1 within the colon carcinoma cell lines dramatically reduced the invasive properties of the cells in vitro. This property was also observed in mice inoculated intracardially with SW620 cells where SOCS1 expression not only reduced the number of animals bearing metastases. Thus, SOCS1 up-regulates expression of E-cadherin to reduce colon cancer cells invasive properties. This pathway could be associated with colorectal cancer survival by reducing the capacity of generating metastases.This project concern 2 replicates in dye-swap of SW620 cells with and without transfected SOCS1 on a 244K custom human genomic expression microarray.
2014-05-01 | E-MTAB-1742 | biostudies-arrayexpress
Project description:Reversion of Alzheimer’s disease signatures
| PRJNA564801 | ENA
Project description:Rationale: Neonatal mice have the capacity to regenerate their hearts in response to injury, but this potential is lost after the first week of life. The transcriptional changes that underpin mammalian cardiac regeneration have not been fully characterized at the molecular level. Objective: The objectives of our study were to determine if myocytes revert the transcriptional phenotype to a less differentiated state during regeneration and to systematically interrogate the transcriptional data to identify and validate potential regulators of this process. Methods and Results: We derived a core transcriptional signature of injury-induced cardiac myocyte regeneration in mouse by comparing global transcriptional programs in a dynamic model of in vitro and in vivo cardiac myocyte differentiation, in vitro cardiac myocyte explant model, as well as a neonatal heart resection model. The regenerating mouse heart revealed a transcriptional reversion of cardiac myocyte differentiation processes including reactivation of latent developmental programs similar to those observed during de-stabilization of a mature cardiac myocyte phenotype in the explant model. We identified potential upstream regulators of the core network, including interleukin 13 (IL13), which induced cardiac myocyte cell cycle entry and STAT6/STAT3 signaling in vitro. We demonstrate that STAT3/periostin and STAT6 signaling are critical mediators of IL13 signaling in cardiac myocytes. These downstream signaling molecules are also modulated in the regenerating mouse heart. Conclusions: Our work reveals new insights into the transcriptional regulation of mammalian cardiac regeneration and provides the founding circuitry for identifying potential regulators for stimulating heart regeneration. Comparison of transcriptional programs of primary myocardial tissues sampled from neonatal mice and murine hearts undergoing post-injury regeneration, along with in vitro ESC-differentiated cardiomyocytes
2014-12-20 | E-GEOD-64403 | biostudies-arrayexpress
Project description:Honey bees move through a series of in-hive tasks (“nursing”) to outside tasks (“foraging”) that coincident with an intense increase in metabolic activity. Social context can cause worker bees to speed up, or slow down this process and foragers may revert back to their earlier in hive tasks accompanied by reversion to earlier physiological states. To determine if the transcriptional profile of forager bees can revert, or if the effects of flight on gene expression are irreversible, we used whole-genome microarrays. Brain tissue and flight muscle exhibited independent patterns of expression during behavioral transitions, with patterns of expression in the brain reflecting both age and behavior, while flight muscle exhibited primarily age-related patterns of expression. Our data suggest that the transition from little to no flight (nurse) to intense flight (forager), rather than the amount of flight has a major effect on gene expression. Following behavioral reversion there was a partial reversion in gene expression but some aspects of forager expression patterns, such as those for genes involved in immune function, remained. These data suggest an epigenetic control and energy balance role in honey bee functional senescence.
2012-10-01 | GSE40650 | GEO
Project description:Rationale: Neonatal mice have the capacity to regenerate their hearts in response to injury, but this potential is lost after the first week of life. The transcriptional changes that underpin mammalian cardiac regeneration have not been fully characterized at the molecular level. Objective: The objectives of our study were to determine if myocytes revert the transcriptional phenotype to a less differentiated state during regeneration and to systematically interrogate the transcriptional data to identify and validate potential regulators of this process. Methods and Results: We derived a core transcriptional signature of injury-induced cardiac myocyte regeneration in mouse by comparing global transcriptional programs in a dynamic model of in vitro and in vivo cardiac myocyte differentiation, in vitro cardiac myocyte explant model, as well as a neonatal heart resection model. The regenerating mouse heart revealed a transcriptional reversion of cardiac myocyte differentiation processes including reactivation of latent developmental programs similar to those observed during de-stabilization of a mature cardiac myocyte phenotype in the explant model. We identified potential upstream regulators of the core network, including interleukin 13 (IL13), which induced cardiac myocyte cell cycle entry and STAT6/STAT3 signaling in vitro. We demonstrate that STAT3/periostin and STAT6 signaling are critical mediators of IL13 signaling in cardiac myocytes. These downstream signaling molecules are also modulated in the regenerating mouse heart. Conclusions: Our work reveals new insights into the transcriptional regulation of mammalian cardiac regeneration and provides the founding circuitry for identifying potential regulators for stimulating heart regeneration.
2014-12-20 | GSE64403 | GEO
Project description:Netrin-1 is up-regulated in a large fraction of human cancers as a pro-tumoralmechanism. Therefore, a phase I trial assessing netrin-1 blockade using an anti- netrin-1 monoclonal antibody (NP137) in patients with advanced solid cancer is ongoing. We analyzed here the potential implication of netrin-1 in endometrial carcinoma. We show that netrin-1 is up-regulated in the vast majority of human endometrial carcinomas, and demonstrate that NP137 treatment is effective in reducing tumor progression in preclinical mouse models of endometrial carcinoma. We report here a confirmed objective response in a patient with endometrial carcinoma (EC) treated in monotherapy with NP137. A 51.16% reduction of target lesions at 6 weeks and up to 54.65% reduction during the next 6 months of NP137 treatment was observed for a 74 years old woman. To evaluate the mechanism of action of the anti-netrin-1 mAb, we performed gene profiling of mouse PTENf/f endometrial tumors treated with NP137 and observed that, in addition to cell death induction, NP137 induced a reversion of the Epithelial-to-Mesenchymal Transition (EMT). Of interest, by analyzing 13 pre/post paired biopsies of the patients with endometrial carcinoma treated in the NP137 trial, we confirmed a significant reduction of EMT in tumors. We thus performed pre/post NP137 treatment biopsy- based single cell RNA sequencing in a patient with endometrial carcinoma, and showed a net decrease of neoplastic cells and a reversion of EMT markers in the remaining tumor cells, with associated change in the tumor microenvironment. Given the importance of EMT in resistance to the current standard of care including chemotherapy or immune-checkpoint inhibitors, we showed in a PTENf/f endometrial cancer mouse model that combining NP137 with carboplatin paclitaxel outperformed carboplatin paclitaxel alone. Our results thus identify for the first time, in preclinical models and in patients, netrin-1 blockade as a clinical strategy triggering both tumor debulking and reversion of EMT, thus potentially alleviating resistance to standard treatments.
2023-06-02 | GSE225687 | GEO
Project description:Netrin-1 is up-regulated in a large fraction of human cancers as a pro-tumoralmechanism. Therefore, a phase I trial assessing netrin-1 blockade using an anti- netrin-1 monoclonal antibody (NP137) in patients with advanced solid cancer is ongoing. We analyzed here the potential implication of netrin-1 in endometrial carcinoma. We show that netrin-1 is up-regulated in the vast majority of human endometrial carcinomas, and demonstrate that NP137 treatment is effective in reducing tumor progression in preclinical mouse models of endometrial carcinoma. We report here a confirmed objective response in a patient with endometrial carcinoma (EC) treated in monotherapy with NP137. A 51.16% reduction of target lesions at 6 weeks and up to 54.65% reduction during the next 6 months of NP137 treatment was observed for a 74 years old woman. To evaluate the mechanism of action of the anti-netrin-1 mAb, we performed gene profiling of mouse PTENf/f endometrial tumors treated with NP137 and observed that, in addition to cell death induction, NP137 induced a reversion of the Epithelial-to-Mesenchymal Transition (EMT). Of interest, by analyzing 13 pre/post paired biopsies of the patients with endometrial carcinoma treated in the NP137 trial, we confirmed a significant reduction of EMT in tumors. We thus performed pre/post NP137 treatment biopsy- based single cell RNA sequencing in a patient with endometrial carcinoma, and showed a net decrease of neoplastic cells and a reversion of EMT markers in the remaining tumor cells, with associated change in the tumor microenvironment. Given the importance of EMT in resistance to the current standard of care including chemotherapy or immune-checkpoint inhibitors, we showed in a PTENf/f endometrial cancer mouse model that combining NP137 with carboplatin paclitaxel outperformed carboplatin paclitaxel alone. Our results thus identify for the first time, in preclinical models and in patients, netrin-1 blockade as a clinical strategy triggering both tumor debulking and reversion of EMT, thus potentially alleviating resistance to standard treatments.
2023-06-02 | GSE225688 | GEO