Transiently enhanced multi-drug resistance by epigenetic mechanism from reprogrammed cancer cell model
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA579059 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10333585.fastq.gz | Fastqsanger.gz | |||
| SRR10333586.fastq.gz | Fastqsanger.gz | |||
| SRR10333587.fastq.gz | Fastqsanger.gz | |||
| SRR10333588.fastq.gz | Fastqsanger.gz | |||
| SRR10333589.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
Similar Datasets
Project description:Background: Drug resistance by epigenetic modulation in cancer cells has been suggested, and the epigenetic-driven heterogeneity has been suggested as an important mechanism. To elucidate the epigenetic mechanism further, epigenetically reprogrammed cancer (R-cancer) cells were established and their resistance during differentiation was analyzed. Methods: R-cancer cells for H460 (R-H460) were established by transient introduction of reprogramming factors. Then, differentiated R-H460 (dR-H460) cells were prepared by withdrawal of stem cell media (SCM) for various durations, and the changes in drug resistance were tested. Results: dR-H460 cells with SCM-withdrawal for about 2 weeks (mdR-H460 cells) formed significantly more drug-resistant colonies to both cisplatin and paclitaxel. The resistant phenotype of the cisplatin resistant colonies from mdR-H460 cells, however, was lost after long-term (about 70-90 days) cisplatin-withdrawal, suggesting a transient epigenetic mechanism. In another R-cancer cell model with N87, the increased drug-resistance was also observed for both cisplatin and paclitaxel after SCM-withdrawal. In single cell analyses, heterogeneity did not increase significantly in mdR-H460, although relatively higher fraction of mdR-H460 cells was observed in several clusters of parent H460 cells. Conclusion: Based on R-cancer model, increased cancer cell population under epigenetic transition, rather than heterogeneity from epigenetic changes, may confer the epigenetic-driven drug resistance, which can provide a new strategy to fight cancers by control of cancer cells under epigenetic transition.
2020-10-22 | GSE139275 | GEO
Project description:Diamond-Blackfan anemia (DBA) is a congenital disorder characterized by the failure of erythroid progenitor differentiation, severely curtailing red blood cell production. Because many DBA patients fail to respond to corticosteroid therapy, there is considerable need for therapeutics for this disorder. Identifying therapeutics for DBA requires circumventing the paucity of primary patient blood stem and progenitor cells. To this end, we adopted a reprogramming strategy to generate expandable hematopoietic progenitor cells from induced pluripotent stem cells (iPSCs) from DBA patients. Reprogrammed DBA progenitors recapitulate defects in erythroid differentiation which were rescued by gene complementation. Unbiased chemical screens identified SMER28, a small molecule inducer of autophagy, which enhanced erythropoiesis in a range of in vitro and in vivo models of DBA. SMER28 acted through autophagy factor ATG5 to stimulate erythropoiesis and upregulate expression of globin genes. These findings present an unbiased drug screen for hematological disease using iPSCs and identify autophagy as a therapeutic pathway in DBA.
2017-01-01 | GSE90940 | GEO
Project description:Human pluripotent stem cells can be rapidly converted into functional neurons by ectopic expression of proneural transcription factors. Here we show that directly reprogrammed neurons, despite their rapid maturation kinetics, can model teratogenic mechanisms that specifically affect early neurodevelopment. We delineated distinct phases of in vitro maturation during reprogramming of human neurons and assessed the cellular phenotypes of valproic acid (VPA), a teratogenic drug. VPA exposure caused chronic impairment of dendritic morphology and functional properties of developing neurons, but not those of mature neurons. These pathogenic effects were associated with VPA-mediated inhibition of the histone deacetylase (HDAC) and glycogen synthase kinase-3 (GSK-3) pathways, which caused transcriptional downregulation of many genes, including MARCKSL1, an actin-stabilizing protein essential for dendritic morphogenesis and synapse maturation during early neurodevelopment. Our findings identify a developmentally restricted pathogenic mechanism of VPA and establish the use of reprogrammed neurons as an effective platform for modeling teratogenic pathways.
2019-05-28 | GSE129241 | GEO
Project description:Enhanced combination treatment on osteosarcoma by mitigating drug-induced oncogenic signaling pathway activation
| PRJNA1166301 | ENA
Project description:Reprogrammed alveolar macrophages after pneumonia recovery
| PRJNA553227 | ENA
Project description:RNA Sequencing for reprogrammed beta cells
| PRJNA417706 | ENA
Project description:Transient plasmid transfection is common approach for studies in cultured mammalian cells. To examine behavior of transfected plasmids, we analyzed their transcriptional landscape by deep sequencing. We found that plasmids generate different levels of transcripts virtually everywhere. Spurious transcription may have undesirable effects as some co-transfected plasmids inhibited expression of luciferase reporters in a dose-dependent manner. In one case, we attributed this effect to kan/neo resistance cassette, which generated a unique population of edited sense and antisense small RNAs. The unexpected complexity of expression of transiently transfected plasmids highlights the importance of appropriate experimental controls. HEK293 cells (human origin) transiently transfected with 4 various plasmids
2012-08-17 | E-GEOD-36062 | biostudies-arrayexpress
Project description:Infections associated with antimicrobial-resistant bacteria now represent a significant threat to human health using conventional therapy, necessitating the development of alternate and more effective antibacterial compounds. Silver nanoparticles (Ag NPs) have been proposed as potential antimicrobial agents to combat infections. A complete understanding of their antimicrobial activity is required before these molecules can be used in therapy. Lysozyme coated Ag NPs were synthesized and characterized by TEMEDS, XRD, UV-vis, FTIR spectroscopy, zeta potential, and oxidative potential assay. Biochemical assays and deep level transcriptional analysis using RNA sequencing were used to decipher how Ag NPs exert their antibacterial action against multi-drug resistant Klebsiella pneumoniae MGH78578. RNAseq data revealed that Ag NPs induced a triclosan-like bactericidal mechanism responsible for the inhibition of the type II fatty acid biosynthesis. Additionally, released AgC generated oxidative stress both extra and intracellularly in K. pneumoniae. The data showed that triclosan-like activity and oxidative stress cumulatively underpinned the antibacterial activity of Ag NPs. This result was confirmed by the analysis of the bactericidal effect of Ag NPs against the isogenic K. pneumoniae MGH78578 1soxS mutant, which exhibits a compromised oxidative stress response compared to the wild type. Silver nanoparticles induce a triclosan like antibacterial action mechanism in multi-drug resistant K. pneumoniae. This study extends our understanding of anti-Klebsiella mechanisms associated with exposure to Ag NPs. This allowed us to model how bacteria might develop resistance against silver nanoparticles, should the latter be used in therapy.
2021-01-31 | GSE151953 | GEO
Project description:RNA-seq analysis of fibromodulin reprogrammed human BJ fibroblasts to obtain the global transcripton of the yield fibromodulin reprogrammed (FReP) cells.
2019-08-10 | GSE104830 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Sustained clinical remission (CR) without drug treatment has not been achieved in patients with rheumatoid arthritis (RA). This implies a substantial difference between CR and the healthy state, but it has yet to be quantified. We report a longitudinal monitoring of the drug response at multi-omics levels in the peripheral blood of patients with RA. Our data reveal that drug treatments alter the molecular profile closer to that of HCs at the transcriptome, serum proteome and immunophenotype level. Patient follow-up suggests that the molecular profile after drug treatments is associated with long-term stable CR. In addition, we identify molecular signatures that are resistant to drug treatments. These signatures are associated with RA independently of known disease severity indexes and are largely explained by the imbalance of neutrophils, monocytes, and lymphocytes. This high-dimensional phenotyping provides a quantitative measure of molecular remission and illustrates a multi-omics approach to understanding drug response.
2018-07-16 | GSE93777 | GEO