Project description:Glioblastoma-derived neural stem (GNS) cells were reprogrammed to induced pluripotent stem (iPS) cells by transgenic expression of OCT4 and KLF4. Gene expression profiling was performed in comparison to normal neural stem (NS) cells reprogrammed in parallel, as well as standard ES cells as an independent reference.
Project description:Glioblastoma-derived neural stem (GNS) cells were reprogrammed to induced pluripotent stem (iPS) cells by transgenic expression of OCT4 and KLF4. Genome-wide DNA methylation status was profiled at 485,000 loci to assess epigenetic erasure and restoration due to reprogramming and redifferentiation to the neural stem (NS) cell state.
Project description:Chromatin accessibility was profiled by ATAC-seq in normal and glioblastoma-derived neural stem (GNS) cells, in self-renewing conditions and in response to differentiation stimulus with bone morphogenic protein (BMP).
Project description:The transcriptional response of normal and glioblastoma-derived neural (GNS) cells was profiled in self-renewing conditions and over a time course of differentiation in the presence of bone morphogenic protein (BMP).
Project description:Glioblastomas grow in a rich neurochemical mileu, but targeting neurochemical signaling as a potential therapeutic avenue for these incurable tumors has been underexplored. Thus, we probed patient derived glioblastoma stem cells with a focused library of neurochemicals, to identify new therapeutic targets. Dopaminergic, serotonergic and cholinergic pathways were found to be active against glioblastoma. In particular, dopamine receptor D4 (DRD4) antagonists selectively inhibited glioblastoma growth in vitro and in vivo, in addition to showing synergistic effect with temozolomide. Small molecule or genetic antagonism of DRD4 suppressed ERK1/2 signaling and impaired autophagic flux causing accumulation of autophagic vacuoles and ubiquitinated proteins, associated with G0/G1 cell cycle arrest. These data suggest a new mechanism for treating glioblastoma through modulating dopamine DRD4 signaling. We used Affymetrix microarrays to characterize the mechanism of action for dopamine receptor D4 antagonist (PNU 96415E) in human glioblastoma derived neural stem cells. We treated the human glioblastoma derived neural stem cells (GNS cells) with PNU 96415E for period of 0h, 24h and 48h and extracted RNA for hybridaization on Affymetrix microarrary (Human gene 1.0 ST array) on two GNS lines.
Project description:Mouse embryonic stem cells were maintained in minimal and chemically-defined culture conditions supporting naive pluripotency. Inhibitors of the Gsk3 (CHIR99021) and Mek/Erk (PD0325901) pathways were withdrawn, cultures maintained for 24 hours, and subsequently sorted by flow cytometry based on fluorescence of a short-half-life Rex1(Zfp42)::GFP reporter into two populations: Rex1-high cells, functionally capable of reversion to naive pluripotency, and Rex1-low cells that have exited the naive state.