Transiently enhanced multi-drug resistance by epigenetic mechanism from reprogrammed cancer cell model
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA579059 | ENA |
REPOSITORIES: ENA
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:Directly Reprogrammed Human Neurons Identify a Pathogenic Mechanism of Valproic Acid at Early Developmental Stages
| PRJNA530578 | ENA
Project description:Molecular mechanism of zero valent iron-enhanced microbial azo reduction in Shewanella decolorationis S12
| PRJNA673394 | 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: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:RNA Sequencing for reprogrammed beta cells
| PRJNA417706 | ENA
Project description:Reprogrammed alveolar macrophages after pneumonia recovery
| PRJNA553227 | ENA
Project description:Epstein-Barr virus(EBV) is associated with malignancies from lymphoid and epithelial origin. In many cases, an incomplete EBV association is noted and confoundswhate role the virus plays in oncogenesis. A number of viral proteins have been shown to interact with epigenetic factors to regulate both viral and host gene expression. Thus, we hypothesize that EBV may inadvertantly induce epigenetic alterations to the host genome that are maintained upon loss of the virus. If proven, these results would broaden EBV's role in tumorigenesis and provide a mechanism for how a tumor virus can act in a "hit-and-run" fashion. We examined EBV-induced epigenetic alterations in a setting of viral redundancy and loss. With mounting evidence that EBV can induce epigenetic alterations, we developed a transient infection model where a clonal derivative (designated cl3) from the CCL185/A549 cell line was infected with a recombinant EBV carrying neomycin resistance cassette in place of the BDLF3 open reading frame. Infected cells were passaged ten times, and then selection pressure was removed for an additional ten passages to allow for viral loss. Three transiently-infected EBV-negative clones were identified by single cell cloning (designated 10-9, 10-10, and 10-14). Uninfected parental clone and cells transfected with pcDNA3 plasmid were passaged alongside the transiently-infected clones. Each sample was analyzed in duplicate.
2012-04-10 | E-GEOD-37048 | biostudies-arrayexpress