Invariant Differential Expression Analysis Reveals Mechanism of Cancer Resistance to Cell Cycle Inhibitors
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE156657 | GEO | 2020/12/31
REPOSITORIES: GEO
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Project description:Graphene has been selected as a candidate for synthetic feeder-free culture substrate guiding human/mouse multipotent stem cell lineage specification, and culturing pluripotent stem cells in a number of studies. However, conventional graphene is not an ideal biomaterial to maintain the pluripotency of human pluripotent stem cells (hPSC) including hESCs/hiPSCs due to its intrinsic hydrophobicity and relatively flat surface topography. Here, we applied morphology-controlled nanocrystalline graphene (NG) coating onto the culture substrates via diffusion-associated synthesis (DAS) process and cultivated hPSCs. It is found that enhanced hydrophilicity and controlled surface roughness of DAS-NG enabled tight focal adhesion of hPSCs onto the DAS-NG coated culture substrate and retained pluripotency for over 2 weeks. It is also found hPSCs grown on DAS-NG shared comparable global gene expression profile with hPSCs grown on mouse embryonic fibroblast (MEF). Importantly, the similarities in cell adhesion gene expression between hPSCs grown on DAS-NG and hPSCs on MEF suggest DAS-NG may provide comparable physical cues with MEF for sustaining pluripotency. Taken together, our findings show a new reliable method for culturing hPSCs in feeder-free condition using DAS-graphene. Human iPSCs and human ESC H9 were seeded onto DAS-NG coated glass, ITO or QU, CVD-grown graphene coated glass, uncoated glass and mitomycin-C treated CF1. Human pluripotent stem cells seeded on each culture substrate were cultured in human embryonic stem cell medium composed of knockout DMEM (GIBCO-10829) supplemented with 20% knockout serum replacement (GIBCO-10828), 1mM L-glutamine, 1% penicillin/streptomycin (PAA-P11-010), 1% MEM-non essential amino acid (PAA-M11-003), 0.1mM beta-mercaptoethanol, and 5ng/ml human basic fibroblast growth factor.
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Project description:The retinoblastoma cell cycle regulator pRb and the two related proteins p107 and p130 are thought to suppress cancer development both by inhibiting the G1/S transition of the cell cycle in response to growth-arrest signals and by promoting cellular differentiation. Here, we investigated the phenotype of Rb family triple knock-out (TKO) embryonic stem cells as they differentiate in vivo and in culture. Confirming the central role of the Rb gene family in cell cycle progression, TKO mouse embryos did not survive past mid-gestation and differentiating TKO cells displayed increased proliferation and cell death. However, patterning and cell fate determination were largely unaffected in these TKO embryos. Furthermore, a number of TKO cells, including in the neural lineage, were able to exit the cell cycle in G1 and terminally differentiate. This ability of Rb family TKO cells to undergo cell cycle arrest was associated with the repression of target genes for the E2F6 transcription factor, uncovering a pRb-independent control of the G1/S transition of the cell cycle. These results show that the Rb gene family is required for proper embryonic development but is not absolutely essential to induce G1 arrest and differentiation in certain lineages. Experiment Overall Design: Genome-wide gene expression was analyzed for wild-type and TKO ESC and EB cells. Three biological replicates were isolated for wild-type ESCs, TKO ESCs, and wild-type EBs, while five biological replicates were isolated for TKO EBs.
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