Project description:This SuperSeries is composed of the following subset Series: GSE35911: Reversal of Aberrant Cancer Methylome and Transcriptome upon Direct Reprogramming of Lung Cancer Cells [Expression] GSE35912: Reversal of Aberrant Cancer Methylome and Transcriptome upon Direct Reprogramming of Lung Cancer Cells [Methylation] Refer to individual Series
Project description:The generation of induced pluripotent stem cells (iPSCs) and the direct conversion approach provide an invaluable resource of cells for disease modeling, drug screening, and patient-specific cell-based therapy. However, while iPSCs are stable and resemble ESCs in their transcriptome, methylome and function, the vast majority of the directly converted cells represent an incomplete reprogramming state as evident by their aberrant transcriptome and transgene dependency. This raises the question of whether complete and stable nuclear reprogramming can be achieved only in pluripotent cells. Here we demonstrate the generation of stable and fully functional induced trophoblast stem cells (iTSCs) by transient expression of Gata3, Tfap2c and Eomes. Similarly to iPSCs, iTSCs underwent a complete and stable reprogramming process as assessed by transcriptome and methylome analyses and functional assays such as the formation of hemorrhagic lesion and placenta contribution. Careful examination of the conversion process indicated that the cells did not go through a transient pluripotent state. These results suggest that complete nuclear reprograming can be attained in non-pluripotent cells.
Project description:DNA methylation reprogramming of primordial germ cells (PGCs) is an essential step that affects the activation and inactivation of certain genes, therefore having a direct impact on the transcriptome of an individual. In this study, we have described the methylome landscape of porcine PGCs, characterizing the genomic elements that resist methylation erasure.
Project description:Non-small cell lung cancer cell (NSCLC) lines were reprogrammed with Yamanaka's cocktail and their methylome and transcriptome were studied and characterized. We compared reprogrammed cells to their respective parent (2 NSCLC and 1 human lung fetal fibroblast) and used H1 as a positive control for pluripotency characteristics. The in vitro differentiated cells were also compared to the reprogrammed cells. All samples have biological triplicates except for differentiated cells.
Project description:Non-small cell lung cancer cell (NSCLC) lines were reprogrammed with Yamanaka's cocktail and their methylome and transcriptome were studied and characterized. We compared reprogrammed cells to their respective parent (2 NSCLC and 1 human lung fetal fibroblast) and used H1 as a positive control for pluripotency characteristics. The in vitro differentiated cells were also compared to the reprogrammed cells. All samples have biological triplicates except for differentiated cells.
Project description:Recent advances in glioblastoma (GBM) studies provide a comprehensive catalog of its genetic aberrations and cellular heterogeneity. However, a solid understanding of genotype-based analysis of cancer pathway dependency and actionable target identification is required to transform GBM treatment into a personalized era. Here, we generated a spectrum of mutant iPSCs harboring frequent GBM mutations with CRISPR/Cas9 and profiled the organoids (LEGO: Laboratory Engineered Glioblastoma Organoid) derived from these iPSCs temporally on transcriptome, methylome, metabolome, lipidome, proteome, and phospho-proteome levels. We found that LEGOs form brain tumors in vivo and recapitulate critical features of human GBM. The multi-omics analysis discovered essential milestones driven by genetic heterogeneity during GBM progressions, such as lineage alteration, methylome rewriting, and metabolome/lipidome reprogramming, in concordance with altered pathway activity and drug response. This study provides a tool and research path to realizing genome-based personalized GBM therapy using novel advanced models.
Project description:Non-small cell lung cancer cell (NSCLC) lines were reprogrammed with Yamanaka's cocktail and their methylome and transcriptome were studied and characterized.
Project description:Non-small cell lung cancer cell (NSCLC) lines were reprogrammed with Yamanaka's cocktail and their methylome and transcriptome were studied and characterized.