Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA134681 | ENA |
REPOSITORIES: ENA
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Project description:Porcine induced pluripotent stem cells (piPSCs) could serve as a great model system for human stem cell pre-clinical research. However, the pluripotency gene network of piPSCs, especially the function for the core transcription factor ESRRB, was poorly understood. Here, we constructed ESRRB-overexpressing piPSCs (ESRRB-piPSCs). Compared with the control piPSCs (CON-piPSCs), the ESRRB-piPSCs showed flat, monolayered colony morphology. Moreover, the ESRRB-piPSCs showed greater chimeric capacity into trophectoderm than CON-piPSCs. We found that ESRRB could directly regulate the expressions of trophoblast stem cell (TSC)-specific markers, including KRT8, KRT18 and CDX2, through binding to their promoter regions. Mutational analysis proved that the N-terminus zinc finger domain is indispensable for ESRRB to regulate the TSC markers. Furthermore, this regulation needs the participation of OCT4. Accordingly, the cooperation between ESRRB and OCT4 facilitates the conversion from pluripotent state to the trophoblast-like state.
2022-02-17 | PXD027539 | Pride
Project description:Conversion of murine extraembryonic trophoblast stem cells into induced pluripotent stem cells
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Project description:Extraembryonic trophoblast stem cells (TSC) can be converted to induced pluripotent stem cells (TSC-iPSCs) by overexpressing Oct4, Sox2, Klf4 and cMyc. TSC lines were derived from mice harboring a doxycycline inducible Oct4 allele and an Oct4-GFP reporter that has been demonstrated to be activated in cells upon acquisition of pluripotency. Oct4-GFP-positive blastocysts were collected at 3.5 dpc and transduced with lentiviruses encoding doxycycline inducible Sox2, Klf4 and cMyc transgenes (4FTSC). 4FTSC lines were passaged 10 times to establish a population of constantly growing, self-renewing TSCs in the presence of FGF4 and fibroblast conditioned media. To induce lineage conversion, 4FTSCs were cultured under ESC/Lif conditions and doxycycline. After 28 days, several colonies displaying ESC-characteristic dome-shaped colony morphology and bright Oct4-GFP fluorescence could be detected. The 4FTSC-derived colonies were isolated mechanically, dissociated by trypsinization, and plated onto MEFs in ESC medium without doxycycline demonstrating the independence of exogenous factors. They will be called TSC-iPSCs (Trophoblast stem cell derived induced pluripotent stem cells). To examine if the extraembryonic lineage-specific mRNA profile was overcome, the gene-expression profiles of TSC-iPSCs and their parental 4FTSCs were analyzed by microarray analyses and compared to control ESCs.
2011-02-01 | E-GEOD-25872 | biostudies-arrayexpress
Project description:Conversion of Fibroblasts into Functional Trophoblast Stem-like Cells
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Project description:Cells of the trophoblast lineage constitute the major part of placental tissues in higher mammals. Recent derivation of human trophoblast stem cells (TSC) from placental cytotrophoblasts (CT) and from blastocyst opens new opportunities for studying development and function of human placenta. Here we report that inhibition of TGF pathway leads to direct and robust conversion of primed human pluripotent stem cells into TSC. The resulting cell lines exhibit self-renewal, are able to differentiate into the main trophoblast lineages, and present RNA and epigenetic profiles that are indistinguishable from the TSC lines derived from placenta or blastocyst. Furthermore, activation of YAP pathway is necessary and sufficient for this conversion.
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Project description:Chavez2009 - a core regulatory network of OCT4 in human embryonic stem cells
A core OCT4-regulated network has been identified as a test case, to analyase stem cell characteristics and cellular differentiation.
This model is described in the article:
In silico identification of a core regulatory network of OCT4 in human embryonic stem cells using an integrated approach.
Chavez L, Bais AS, Vingron M, Lehrach H, Adjaye J, Herwig R
BMC Genomics, 2009, 10:314
Abstract:
BACKGROUND: The transcription factor OCT4 is highly expressed in pluripotent embryonic stem cells which are derived from the inner cell mass of mammalian blastocysts. Pluripotency and self renewal are controlled by a transcription regulatory network governed by the transcription factors OCT4, SOX2 and NANOG. Recent studies on reprogramming somatic cells to induced pluripotent stem cells highlight OCT4 as a key regulator of pluripotency.
RESULTS: We have carried out an integrated analysis of high-throughput data (ChIP-on-chip and RNAi experiments along with promoter sequence analysis of putative target genes) and identified a core OCT4 regulatory network in human embryonic stem cells consisting of 33 target genes. Enrichment analysis with these target genes revealed that this integrative analysis increases the functional information content by factors of 1.3 - 4.7 compared to the individual studies. In order to identify potential regulatory co-factors of OCT4, we performed a de novo motif analysis. In addition to known validated OCT4 motifs we obtained binding sites similar to motifs recognized by further regulators of pluripotency and development; e.g. the heterodimer of the transcription factors C-MYC and MAX, a prerequisite for C-MYC transcriptional activity that leads to cell growth and proliferation.
CONCLUSION: Our analysis shows how heterogeneous functional information can be integrated in order to reconstruct gene regulatory networks. As a test case we identified a core OCT4-regulated network that is important for the analysis of stem cell characteristics and cellular differentiation. Functional information is largely enriched using different experimental results. The de novo motif discovery identified well-known regulators closely connected to the OCT4 network as well as potential new regulators of pluripotency and differentiation. These results provide the basis for further targeted functional studies.
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2005-01-01 | MODEL1305010000 | BioModels
Project description:ATAC-seq analysis revealed similarity/dissimilarity in chromatin accessibility between human blastocyst derived trophoblast stem cells (hbdTSCs), human foreskin fibroblasts (HFFs) and pluripotent stem cells (hESCs) compared with HFFs which underwent 3 days of ectopic expression of GATA3, OCT4, KLF4, MYC (GOKM) or OCT4, SOX2, KLF4 and MYC (OSKM).
2023-02-21 | GSE182012 | GEO
Project description:Cells of the trophoblast lineage constitute the major part of placental tissues in higher mammals. Recent derivation of human trophoblast stem cells (TSC) from placental cytotrophoblasts (CT) and from blastocyst opens new opportunities for studying development and function of human placenta. Here we report that inhibition of TGF pathway leads to direct and robust conversion of primed human pluripotent stem cells into TSC. The resulting cell lines exhibit self-renewal, are able to differentiate into the main trophoblast lineages, and present RNA and epigenetic profiles that are indistinguishable from the TSC lines derived from placenta or blastocyst. Furthermore, activation of YAP pathway is necessary and sufficient for this conversion.
2022-09-21 | GSE192917 | GEO
Project description:Direct conversion of fibroblasts into stably expandable neural stem cells
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Project description:Extraembryonic trophoblast stem cells (TSC) can be converted to induced pluripotent stem cells (TSC-iPSCs) by overexpressing Oct4, Sox2, Klf4 and cMyc.
2011-02-01 | GSE25872 | GEO