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Gene expression profiling of GSK3 inhibitor (CHIR99021)-treated intestinal organoids

ABSTRACT: Gene expression profiling of GSK3 inhibitor (CHIR99021)-treated intestinal organoids

PROVIDER: PRJNA433318 | ENA |

REPOSITORIES: ENA

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Human cortical organoids. Chronic treatment with GSK3 inhibitor CHIR99021. Bulk RNAseq.

Project description:Here we used human cortical brain organoids to probe the longitudinal impact of GSK3 inhibition through multiple developmental stages. Chronic GSK3 inhibition increased the proliferation of neural progenitors and caused massive derangement of cortical tissue architecture. Cortical organoids were differentiated as previously described (Paşca et al., 2015, doi: 10.1038/nmeth.3415.).Chronic GSK3 inhibition was performed by adding CHIR99021 (Merck SML1046) to the medium at day 0 (1 microM) and kept throughout the differentiation process until reaching the respective collection timepoints (day 18, day 50, day 100).

2020-06-04 | E-MTAB-8325 | biostudies-arrayexpress

Bulk RNA-seq of human cortical organoids treated with GSK3 inhibitor CHIR99021

Project description:Bulk RNA-seq of human cortical organoids treated with GSK3 inhibitor CHIR99021

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Single cell RNAseq of human cortical organoids investigating the effect of chronic treatment with GSK3 inhibitor CHIR99021

Project description:Here we used human cortical brain organoids to probe the longitudinal impact of GSK3 inhibition through multiple developmental stages. Chronic GSK3 inhibition increased the proliferation of neural progenitors and caused massive derangement of cortical tissue architecture. Cortical organoids were differentiated as previously described (Paşca et al., 2015, doi: 10.1038/nmeth.3415.). Chronic GSK3 inhibition was performed by adding CHIR99021 (Merck SML1046) to the medium at day 0 (1 microM) and kept throughout the differentiation process until reaching the respective collection timepoints (day 50, day 100).

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Gene expression profiling of GSK3 inhibitor (CHIR99021)-treated intestinal organoids

Project description:Acting downstream of many growth factors, extracellular signal-regulated kinase (ERK) plays a pivotal role in regulating cell proliferation and tumorigenesis, where its spatiotemporal dynamics, as well as its strength, determine cellular responses. Here, we uncover the ERK activity dynamics in intestinal epithelial cells (IECs) and their association with tumour characteristics. In vivo imaging identified two distinct modes of ERK activity, sustained and pulse-like activity, in IECs. The sustained and pulse-like activity depended on ErbB2 and EGFR, respectively. Notably, deregulated activation of Wnt signalling, the earliest event in intestinal tumorigenesis, augmented EGFR signalling and exalted it to a dominant driver of ERK activity dynamics, which rendered IECs addicted to EGFR signalling. Furthermore, the frequency of ERK activity pulses was also increased to promote cell proliferation. Thus, ERK activity dynamics are defined by composite inputs from EGFR and ErbB2 signalling in IECs and their alterations underlie tumour-specific sensitivity to pharmacological EGFR inhibition. In this microarray analysis, we aimed to elucidate molecular mechanisms that mediate Wnt signalling activation-induced alterations in EGFR-ERK signalling dynamics.

2018-02-08 | GSE110257 | GEO

RNA-Seq for transcriptome analysis of germinal center B cells upon GSK3 inhibition

Project description:To compare transcriptional changes of germinal center B cells upon GSK3 inhibition, induced GC B cells were treated with GSK3 inhibitor, CHIR99021. 407 differentially expressing genes were identified

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Gene expression profiling of mouse embryonic kidney (E12.5) treated with CHIR99021 or DMSO

Project description:Purpose: To investigate GSK3 inhibitor effect on gene expression during renal development. Methods: mRNA profiles of in-vitro organ culture of mouse embryonic kidney (E12.5) treated with 5 µM CHIR99021 or 0.1% DMSO for 72 hours were generated by deep sequencing in quadruplicate. Results: When comparing CHIR99021 group to DMSO group, in 30890 genes tested, 950 genes were upregulated, and 1,879 genes were downregulated, with a fold change ≥2 and p (padj value) <0.05.

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Transcriptional responses to GSK3 inhibitor and MEK inhibitor on 2i-adapted mouse embryonic stem cells

Project description:The objective of this study was to investigate the roles of GSK3 inhibitor CHIR99021 and MEK inhibitor PD0325901 on 2i-adapted mouse embryonic stem cells (ESCs) in serum-free conditions.Canonical Wnt signaling supports the pluripotency of mouse ESCs but also promotes differentiation of early mammalian cell lineages. To explain these paradoxical observations, we explored the gene regulatory networks at play. Canonical Wnt signaling is intertwined with the pluripotency network comprising Nanog, Oct4, and Sox2 in mouse ESCs. In defined media supporting the derivation and propagation of mouse ESCs, Tcf3 and β-catenin interact with Oct4; Tcf3 binds to Sox motif within Oct-Sox composite motifs that are also bound by Oct4-Sox2 complexes. Further, canonical Wnt signaling up-regulates the activity of the Pou5f1 distal enhancer via the Sox motif in mouse ESCs. When viewed in the context of published studies on Tcf3 and β-catenin mutants, our findings suggest that Tcf3 counters pluripotency by competition with Sox2 at these sites, and Tcf3 inhibition is blocked by β-catenin entry into this complex. Wnt pathway stimulation also triggers β-catenin association at regulatory elements with classic Lef/Tcf motifs associated with differentiation programs. The failure to activate these targets in the presence of a MEK/ERK inhibitor essential for mouse ESC culture suggests that MEK/ERK signaling and canonical Wnt signaling combine to mouse promote ESC differentiation. Triplicates of mouse embryonic stem cells cultured under the following conditions: 1) CHIR99021+PD0325901+LIF; 2) CHIR99021+PD0325901; 3) CHIR99021; 4) PD0325901; 5) DMSO

2013-03-01 | E-GEOD-43421 | biostudies-arrayexpress

Genome-wide analysis of gene expression in LIF and LIF plus CHIR99021 in C57BL/6 mouse embryonic stem cells(B6 mESCs)

2013-08-29 | E-GEOD-50393 | biostudies-arrayexpress