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Qualitative modeling identifies IL-11 as a novel regulator in maintaining self-renewal in human pluripotent stem cells

ABSTRACT: A systems biology approach in which qualitative modeling based on combining boolean networks and in silico perturbation experiments were employed to identify 15 pluripotency regulating cytokines or cytokine related genes. IL-11 was validated as a novel factor capable of maintaing the undifferentiated state of human embryonic stem cells in the absence of exogenously added bFGF to the culture acting via a different mechanims than bFGF. Transcriptomic microarray data of eight overexpression and knock-down experiments were used for qualitative modeling based on boolean networks to predict novel factors - mainly cytokines - that maintain pluripotent human embryonic stem cells in the absence of bFGF in culture. The culture was maintained for at least 9 passages using and stained positive for alcaline phosphatase staining, OCT3/4, SOX2, NANOG, TRA1-60. Microarray based gene expression profiling showed that the IL-11 treatment occupies an intermediate state, between bFGF treatment and the negative control which is no cytokine treatment as judged by hierarchical clustering. Moreover, KEGG pathway analysis indicates common and additional distinct mechanisms of bFGF and IL-11 dependant pluripotency dependant mechanisms.

ORGANISM(S): Homo sapiens

SUBMITTER: Raed Abu Dawud

PROVIDER: E-GEOD-51159 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Qualitative modeling identifies IL-11 as a novel regulator in maintaining self-renewal in human pluripotent stem cells

Project description:A systems biology approach in which qualitative modeling based on combining boolean networks and in silico perturbation experiments were employed to identify 15 pluripotency regulating cytokines or cytokine related genes. IL-11 was validated as a novel factor capable of maintaing the undifferentiated state of human embryonic stem cells in the absence of exogenously added bFGF to the culture acting via a different mechanims than bFGF.

2013-09-26 | GSE51159 | GEO

Comparable mRNA expression of pluripotency-related genes in SNUhES3 cells cultured on autofeeder or xenofeeder system

2011-02-02 | GSE26993 | GEO

Homo sapiens

Project description:Qualitative modeling identifies IL-11 as a novel regulator in maintaining self-renewal in human pluripotent stem cells

| PRJNA221368 | ENA

Comparable mRNA expression of pluripotency-related genes in SNUhES3 cells cultured on autofeeder or xenofeeder system

Project description:I developed a new culture system for hES cells; this system does not require supplementation with bFGF to obtain hES cells that are suitable for tissue engineering and regenerative medicine. This culture system employed mesenchymal stem cells derived from hES cells (hESC-MSCs) as autologous human feeder cells in the absence of bFGF. For pluripotency-related gene expression profiling, a cDNA microarray analysis was performed SNUhES3 cultured on the autofeeder hESC-MSCs layer maintained the undifferentiated state for 30 passages in a manner similar to the SNUhES3 cells on xenofeeder STO cell layer. To compare the pluripotency-related genes in SNUhES3 cells cultured on autofeeder or xenofeeder system, I used agilent one-color array. Two independant experiment performed.

2011-02-02 | E-GEOD-26993 | biostudies-arrayexpress

Effect of FGFC on human embryonic stem cells

Project description:Fibroblast growth factors (FGFs) are essential for maintaining self-renewal in human embryonic stem cells and induced pluripotent stem cells. Recombinant basic FGF (bFGF or FGF2) is conventionally used to culture pluripotent stem cells; however, because of bFGF instability, repeated addition of fresh bFGF into the culture medium is required in order to maintain its concentration. In this study, we demonstrate that a heat-stable chimeric variant of FGF, FGFC, can be successfully used for maintaining human pluripotent stem cells. FGFC is a chimeric protein composed of human FGF1 and FGF2 domains that exhibits higher thermal stability and protease resistance than do both FGF1 and FGF2. Both human embryonic stem cells and induced pluripotent stem cells were maintained in ordinary culture medium containing FGFC instead of FGF2. Comparison of cells grown in FGFC with those grown in conventional FGF2 media, showed no significant differences in terms of the expression of pluripotency markers, global gene expression, karyotype, or differentiation potential into the three germ lineages. We therefore propose FGFC, as an effective alternative to FGF2, for maintenance of human pluripotent stem cells.

2017-02-09 | GSE55428 | GEO

Characterization of Interleukin 11-producing fibroblasts that constitute a niche for tumor development [Agilent]

Project description:Interleukin (IL)-11 belongs to a member of the IL-6 family of cytokines and is involved in a variety of cellular responses. However, the origin and functions of IL-11-producing (IL-11+) cells are not fully understood. To characterize IL-11+ cells in vivo, we generated Il11 reporter mice. IL-11+ cells rapidly appeared in the colon of mice after dextran sulfate sodium treatment. IL-11+ cells expressed fibroblast markers and genes associated with cell proliferation and tissue repair. IL-11+ cells also appeared in the colon of three murine tumor models and human colorectal cancers. Deletion of Il11ra1 or Il11 attenuated the development of colitis-associated colorectal cancers in mice. IL-11 induced STAT3 phosphorylation in colonic fibroblasts, and injection of IL-11 receptor agonist upregulated many genes that were enriched in IL-11+ cells. Together, tumor cells induced IL-11+ fibroblasts, and a feed-forward loop between IL-11 and IL-11+ fibroblasts might constitute a niche for promoting tumor development.

2021-02-22 | GSE141643 | GEO

Genome-wide analysis of interleukin (IL) -6 and IL-11 responsive genes in murine gastric tumors

Project description:We performed micrarrays to analyse gene expression in spontaneously arising gastric tumors from gp130Y757F/F mutant mice (Tebbutt et al., 2002) following administration of recombinant human IL-6 or IL-11. The present study was designed to assess differences in gene expression in response to IL-6 and IL-11, two cytokines which both activate the shared gp130 receptor and downstream Stat3 signalling pathway. Since gastric tumorigenesis in gp130Y757F/F mice is strictly dependent on IL-11, but not IL-6 signalling (Ernst et al., 2008) the study aimed to identify IL-6 and IL-11 specific target genes which may account for the IL-11 dependent tumor development.

2013-08-10 | GSE43800 | GEO

Proteomic analysis of human eosinophils stimulated with IL-4 and IL-5

Project description:Activated eosinophils is a major cell type to be involved in allergic diseases. Type 2 cytokines (IL-4 and IL-5) are important to establish and augment their inflammatory process. The aim of this study is to clarify the role of these cytokines as direct activators for human eosinophils.

2024-06-20 | PXD052200 | JPOST Repository

Interleukin-11-expressing fibroblasts have a unique gene signature correlated with poor prognosis of colorectal cancer

Project description:Interleukin (IL)-11 is a member of the IL-6 family of cytokines and involved in multiple cellular responses, including tumor development. However, the origin and functions of IL-11-producing (IL-11+) cells are not fully understood. To characterize IL-11+ cells in vivo, we generated Il11 reporter mice. IL-11+ cells appeared in the colon of murine tumor and acute colitis models. Il11ra1 or Il11 deletion attenuated the development of colitis-associated colorectal cancer. IL-11+ cells expressed fibroblast markers, and genes associated with cell proliferation and tissue repair. IL-11 induced the activation of colonic fibroblasts and epithelial cells through phosphorylation of STAT3. Human cancer database analysis revealed that a set of genes enriched in IL-11+ fibroblasts was elevated in human colorectal cancer, and correlated with reduced recurrence-free survival. Together, IL-11+ fibroblasts activate both tumor cells and fibroblasts via secretion of IL-11, thereby constituting a feed forward loop between tumor cells and fibroblasts in the tumor microenvironment.

2021-02-22 | GSE164232 | GEO

RNA sequencing of spheroids from HUVECs for differences in Cis- and Trans-signaling of IL-11

Project description:Cytokines of the IL-6 family, such as IL-11, may influence angiogenesis. Our experiments showed opposite angiogenic effects on HUVECs depending on cis- or transsignaling of IL-11. Spheroids from the 3D angiogenesis model (spheroid sprouting assay) were lysed in QIAzole buffer by vigorous vortexing. The transcriptomic changes were analyzed by RNA sequencing.

2024-09-20 | GSE234142 | GEO

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