ChIP-seq and RNA-seq analyses identify Wnt and Fgf signaling pathways as Prep1 targets in mouse embryonic stem cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE63282 | GEO | 2015/04/01
SECONDARY ACCESSION(S): PRJNA267191
REPOSITORIES: GEO
Similar Datasets
Project description:The Prep1 (Pknox1) homeodomain transcription factor is essential at multiple stages of embryo development. In the E11.5 embryo trunk, we previously estimated that Prep1 binds about 3,300 genomic sites at a highly specific decameric consensus sequence, mainly governing basal cellular functions. We now show that in embryonic stem (ES) cells Prep1 binding pattern only partly overlaps that of the embryo trunk, with about 2,000 novel sites, highlighting a change of targets between embryonic differentiated v. embryonic stem cells. RNA-seq identifies about 1800 genes down-regulated in Prep1- /- ES cells which belong to gene ontology categories not enriched in the E11.5 Prep1i/i differentiated embryo, including in particular the Wnt and Fgf pathways. Indeed, we find aberrant Wnt and Fgf expression levels in the Prep1-/- ES cells which agrees with a deficient embryoid bodies (EBs) differentiation. Re-establishment of the Prep1 level rescues the phenotype. [ChIP-Seq] Examination of genome-wide Prep1 binding in mouse ES cells using ChIP-seq and Illumina GAII sequencing. [RNA-Seq] Examination of gene expression in wild type and Prep1-/- mouse ES cells using RNA-seq and Illumina GAII sequencing.
2015-04-01 | E-GEOD-63282 | biostudies-arrayexpress
Project description:Both FGF and WNT pathways play important roles in embryonic development, stem cell self-renewal and are frequently deregulated in breast cancer. To study the cooperation between FGF and WNT signaling, we have generated a mouse model, MMTV-WNT1/MMTV-iFGFR1 (WNT/iR1), in which we could chemically overactivate iFGFR1 in a ligand-independent manner.
2017-11-22 | MSV000081730 | MassIVE
Project description:The formation of the vertebrate body is driven by the progressive and coordinated production of trunk tissues from pools of progenitors located in the posterior of the embryo. Aspects of this process are recapitulated by in vitro models based on pluripotent stem cells (PSCs). However, these models lack several tissue components normally found in the vertebrate trunk. Most strikingly, the notochord, a hallmark of chordates and the source of midline signals that pattern surrounding tissues, is absent from current models of human trunk formation. To investigate how trunk tissue is formed, we performed single-cell transcriptomic analysis of chick embryos. This delineated molecularly discrete progenitor populations, which we spatially locate in the embryo and relate to signalling activity. Guided by this map, we determined how a stereotypical spatial organization of tissue types arises in differentiating human PSCs. This involved LATS1/2 mediated repression of YAP activity facilitating WNT signalling, that, together with FGF mediated ERK1/2 activation, induces the transcription factor Bra/TBXT. In addition, timely inhibition of a WNT-induced NODAL and BMP signalling cascade regulates the proportions of different tissue types produced, including notochordal cells. We exploit this to develop an integrated 3D model of human notochord and neural tissue formation. Together the data provide insight into the mechanisms responsible for the formation of the tissues that comprise the vertebrate trunk and pave the way for future studies of patterning in a tissue-like environment.
2024-02-14 | GSE255338 | GEO
Project description:The formation of the vertebrate body is driven by the progressive and coordinated production of trunk tissues from pools of progenitors located in the posterior of the embryo. Aspects of this process are recapitulated by in vitro models based on pluripotent stem cells (PSCs). However, these models lack several tissue components normally found in the vertebrate trunk. Most strikingly, the notochord, a hallmark of chordates and the source of midline signals that pattern surrounding tissues, is absent from current models of human trunk formation. To investigate how trunk tissue is formed, we performed single-cell transcriptomic analysis of chick embryos. This delineated molecularly discrete progenitor populations, which we spatially locate in the embryo and relate to signalling activity. Guided by this map, we determined how a stereotypical spatial organization of tissue types arises in differentiating human PSCs. This involved LATS1/2 mediated repression of YAP activity facilitating WNT signalling, that, together with FGF mediated ERK1/2 activation, induces the transcription factor Bra/TBXT. In addition, timely inhibition of a WNT-induced NODAL and BMP signalling cascade regulates the proportions of different tissue types produced, including notochordal cells. We exploit this to develop an integrated 3D model of human notochord and neural tissue formation. Together the data provide insight into the mechanisms responsible for the formation of the tissues that comprise the vertebrate trunk and pave the way for future studies of patterning in a tissue-like environment.
2023-03-06 | GSE223189 | GEO
Project description:The formation of the vertebrate body is driven by the progressive and coordinated production of trunk tissues from pools of progenitors located in the posterior of the embryo. Aspects of this process are recapitulated by in vitro models based on pluripotent stem cells (PSCs). However, these models lack several tissue components normally found in the vertebrate trunk. Most strikingly, the notochord, a hallmark of chordates and the source of midline signals that pattern surrounding tissues, is absent from current models of human trunk formation. To investigate how trunk tissue is formed, we performed single-cell transcriptomic analysis of chick embryos. This delineated molecularly discrete progenitor populations, which we spatially locate in the embryo and relate to signalling activity. Guided by this map, we determined how a stereotypical spatial organization of tissue types arises in differentiating human PSCs. This involved LATS1/2 mediated repression of YAP activity facilitating WNT signalling, that, together with FGF mediated ERK1/2 activation, induces the transcription factor Bra/TBXT. In addition, timely inhibition of a WNT-induced NODAL and BMP signalling cascade regulates the proportions of different tissue types produced, including notochordal cells. We exploit this to develop an integrated 3D model of human notochord and neural tissue formation. Together the data provide insight into the mechanisms responsible for the formation of the tissues that comprise the vertebrate trunk and pave the way for future studies of patterning in a tissue-like environment.
2023-03-06 | GSE224404 | GEO
Project description:Primitive neural stem cells (NSCs) could be derived from pluripotent mouse embryonic stem (ES) cells, and then differentiate into definitive-type neural stem cells which resemble NSCs obtained from the central nervous system. Hence, primitive NSCs define an early stage of neural induction and provide a model to understand the mechanism that controls initial neural commitment. In this study, we performed microarray assay to analyze the global transcriptional profiles in mouse ES cell-derived primitive and definitive NSCs and to depict the molecular changes during the multi-staged neural differentiation process. Primitive NSCs derived directly from ESCs in Lif (p-NSC_L), primitive NSCs that were sub-cultured in the presence of Lif and FGF (p-NSC_LF), as well as definitive NSCs derived from primitive NSCs in medium containing FGF and EGF, were collected for RNA extraction and hybridization on Affymetrix microarrays. Mouse ESCs and NSCs obtained from mouse embryonic brain (E11.5) were included for controls. For each cell type, we collected two biological replicate samples for microarray analysis.
2014-03-01 | E-GEOD-44608 | biostudies-arrayexpress
Project description:Meis, Prep and Pbx1 TALE homeoproteins interactions with Hox proteins are essential for development and disease. Although Meis and Prep behave similarly in vitro, their in vivo activities remain largely unexplored. We show that Prep and Meis interact with largely independent sets of genomic sites and select different DNA binding sequences, with Prep associating mostly with promoters and house-keeping genes and Meis with promoter-remote regions and developmental genes. Hox target sequences associate strongly with Meis but not with Prep binding sites, while Pbx1 cooperates with both Prep and Meis. Accordingly, Meis1 shows strong genetic interaction with Pbx1 but not with Prep1. Meis1 and Prep1 nonetheless co-regulate a subset of genes, predominantly through opposing effects. Notably, the TALE homeoprotein binding profile subdivides Hox clusters into two domains differentially regulated by Meis1 and Prep1. After duplication of the ancestral gene, Meis and Prep thus specialized their interactions but maintained significant regulatory coordination. RNA-seq of 2 Meis1 and Prep1 loss of function mutants in E11.5 C57BL/6 embryonic mice
2013-03-31 | E-GEOD-39605 | biostudies-arrayexpress
Project description:This is the simple model without diffusion described in th epublication
Sharp developmental thresholds defined through bistability by antagonistic gradients of retinoic acid and FGF signaling.
Goldbeter A, Gonze D, Pourquié O. Dev Dyn. 2007 Jun;236(6):1495-508. PMID:
17497689, doi:10.1016/j.jtbi.2008.01.006
Abstract:
The establishment of thresholds along morphogen gradients in the embryo is poorly understood. Using mathematical modeling, we show that mutually inhibitory gradients can generate and position sharp morphogen thresholds in the embryonic space. Taking vertebrate segmentation as a paradigm, we demonstrate that the antagonistic gradients of retinoic acid (RA) and Fibroblast Growth Factor (FGF) along the presomitic mesoderm (PSM) may lead to the coexistence of two stable steady states. Here, we propose that this bistability is associated with abrupt switches in the levels of FGF and RA signaling, which permit the synchronized activation of segmentation genes, such as mesp2, in successive cohorts of PSM cells in response to the segmentation clock, thereby defining the future segments. Bistability resulting from mutual inhibition of RA and FGF provides a molecular mechanism for the all-or-none transitions assumed in the "clock and wavefront" somitogenesis model. Given that mutually antagonistic signaling gradients are common in development, such bistable switches could represent an important principle underlying embryonic patterning.
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This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
For more information see the terms of use.
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2010-11-17 | BIOMD0000000275 | BioModels
Project description:Embryonic stem (ES) cells have a remarkable capacity to self-organize complex, multi-layered optic cups in vitro via a culture technique called SFEBq. During both SFEBq and in vivo optic cup development, Rax (Rx) expressing neural retina epithelial (NRE) tissues utilize Fgf and Wnt/β-catenin signalling pathways to differentiate into neural retina (NR) and retinal-pigmented epithelial (RPE) tissues, respectively. How these signaling pathways affect gene expression during optic tissue formation has remained largely unknown, especially at the transcriptome scale. We generated Day 10 Rx+ optic tissue using SFEBq, exposed these tissues to either Fgf or Wnt/β-catenin stimulation, and assayed their gene expression at Days 12 and 15 using RNA-Seq. We measured gene expression in these 5 sample groups in biological triplicate using RNA-seq (Illumina HiSeq) .
2015-05-18 | E-GEOD-62432 | biostudies-arrayexpress
Project description:Meis, Prep and Pbx1 TALE homeoproteins interactions with Hox proteins are essential for development and disease. Although Meis and Prep behave similarly in vitro, their in vivo activities remain largely unexplored. We show that Prep and Meis interact with largely independent sets of genomic sites and select different DNA binding sequences, with Prep associating mostly with promoters and house-keeping genes and Meis with promoter-remote regions and developmental genes. Hox target sequences associate strongly with Meis but not with Prep binding sites, while Pbx1 cooperates with both Prep and Meis. Accordingly, Meis1 shows strong genetic interaction with Pbx1 but not with Prep1. Meis1 and Prep1 nonetheless co-regulate a subset of genes, predominantly through opposing effects. Notably, the TALE homeoprotein binding profile subdivides Hox clusters into two domains differentially regulated by Meis1 and Prep1. After duplication of the ancestral gene, Meis and Prep thus specialized their interactions but maintained significant regulatory coordination. ChIP-seq of 3 TALE proteins in E11.5 C57BL/6 embryonic mice
2013-03-31 | E-GEOD-39608 | biostudies-arrayexpress