Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Global identification of retinoic acid regulated genes

ABSTRACT: Retinoic acid (RA) signaling plays a major role in controlling several developmental processes in vertebrate embryos. RA repression of caudal Fgf8 has emerged as a crucial mechanism through which RA controls body axis extension, somitogenesis, and spinal cord neurogenesis. The role of RA in Fgf8 repression is supported by mechanistic studies demonstrating direct RA repression through a nearby RA response element that recruits NCOR in an RA-dependent manner. RA is also required for balanced neuromesodermal progenitor differentiation needed for coordinated generation of mesodermal progenitors for somites and neural progenitors for spinal cord. As many pathways are controlled by RA, we performed RNA-seq analysis comparing wild-type embryos with Aldh1a2 mutants that lack the ability to produce RA. This analysis identified a few hundred genes whose expression is significantly altered when RA is absent, thus providing candidate genes for further analysis to discover RA-regulated genes essential for development.

ORGANISM(S): Mus musculus

PROVIDER: GSE131584 | GEO | 2019/05/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Global identification of retinoic acid regulated enhancers and silencers

Project description:Retinoic acid (RA) is known to regulate many genes during development by acting as a ligand for nuclear RA receptors that bind RA response elements (RAREs). However, identification of RAREs required to activate or repress specific genes during development has been quite difficult. Here, we focused on identification of RAREs in the developing trunk of vertebrate embryos during the early stages of body axis extension when RA controls neuromesodermal progenitor differentiation, spinal cord neurogenesis, somitogenesis, and forelimb bud initiation. Trunks from wild-type and Aldh1a2-/- mutants lacking RA synthesis were compared using ChIP-seq analysis for H3K27ac (a marker of gene activation) and H3K27me3 (a marker of gene repression) as well as RNA-seq analysis. We identified numerous RAREs, defined as elements displaying differential deposition of H3K27ac and/or H3K27me3 marks in Aldh1a2-/- vs wild-type that contain a canonical RARE sequence and are near genes that have altered expression when RA is missing. Our findings were able to differentiate genes likely to be directly regulated by RA via a RARE versus genes regulated by another factor further downstream. We identified several RA-regulated genes associated with changes in both H3K27ac and H3K27me3 near a RARE, providing new insight into how RAREs function in vivo.

2019-05-23 | GSE131624 | GEO

Sustained experimental activation of FGF8/ERK in the developing chicken spinal cord reproducibly models early events in ERK-mediated tumorigenesis

Project description:Most human cancers demonstrate activated MAPK/ERK pathway signaling as a key tumor initiation step, but the immediate steps of further oncogenic progression are poorly understood due to a lack of appropriate models. Spinal cord differentiation follows caudal elongation in vertebrate embryos; both processes are regulated by a FGF8 gradient highest in neuromesodermal progenitors (NMP), where kinase effectors ERK1/2 maintain an undifferentiated state. FGF8/ERK signal attenuation is necessary for NMPs to progress to differentiation. We show that sustained ERK1/2 activity, using a constitutively active form of the kinase MEK1 (MEK1ca) in the chicken embryo, reproducibly provokes neopasia in the developing spinal cord. Transcriptomic data show that neoplasia not only relies on the maintenance of NMP gene expression, and the inhibition of genes expressed in the differentiating spinal cord, but also on a profound change in the transcriptional signature of the spinal cord cells leading to a complete loss of cell-type identity. MEK1ca expression in the developing spinal cord of the chicken embryo is therefore a tractable in vivo model to identify the critical factors fostering malignancy in ERK-induced tumorigenesis.

2021-08-17 | GSE182072 | GEO

Retinoic acid mediated neural and mesoderm specification during vertebrate trunk development

Project description:Neuromesodermal progenitors are located in the caudal lateral epiblast region of embryos and are important for the generation of spinal cord and somite tissue that forms the vertebrate body. In this study we use single cell transcriptomics to define the molecular signature of in vivo and in vitro NMPs and reverse engineer the mechanism that regulates their differentiation towards the neural and mesodermal lineage.

2017-03-22 | E-MTAB-5208 | biostudies-arrayexpress

RNA-seq analysis of retinoic acid treated mouse neuromesodermal progenitors

Project description:Bipotent neuromesodermal progenitors (NMPs) residing in the caudal epiblast drive coordinated body axis extension by generating both posterior neuroectoderm and presomitic mesoderm. Retinoic acid (RA) is required for body axis extension, however the early molecular response to RA signaling is poorly defined, as is its relationship to NMP biology. As endogenous RA is first seen near the time when NMPs appear, we used WNT/FGF agonists to differentiate embryonic stem cells to NMPs which were then treated with a short 2-h pulse of 25 nM RA or 1 µM RA followed by RNA-seq transcriptome analysis. Differential expression analysis of this dataset indicated that treatment with 25 nM RA, but not 1 µM RA, provided physiologically relevant findings. The 25 nM RA dataset yielded a cohort of previously known caudal RA target genes including Fgf8 (repressed) and Sox2 (activated), plus novel early RA signaling targets with nearby conserved RA response elements. Importantly, validation of top-ranked genes in vivo using RA-deficient Raldh2-/- embryos identified novel examples of RA activation (Nkx1-2, Zfp503, Zfp703, Gbx2, Fgf15, Nt5e) or RA repression (Id1) of genes expressed in the NMP niche or progeny. These findings provide evidence for early instructive and permissive roles of RA in controlling differentiation of NMPs to neural and mesodermal lineages.

2016-12-22 | GSE83251 | GEO

Generation and characterisation of pre-neural progenitors and neural crest from human embryonic stem cells.

Project description:The spinal cord emerges from a niche of neuromesodermal progenitors (NMPs) formed and maintained by Wnt/FGF signals in the posterior end of the embryo. NMP-like cells can be generated from human pluripotent stem cells providing a promising source for spinal cord replacement therapies. However, these progenitors are often transient and unable to produce the full range of rostrocaudal spinal cord identities in vitro. Here we report the generation of NMP-derived pre-neural progenitors (PNPs). These PNPs maintain pre-spinal cord identity by co-expressing the transcription factors SOX2 and CDX2, while losing the mesodermal potential of NMPs by downregulating TBXT. They gradually adopt more posterior identity by activating collinear HOX gene expression, and in parallel undergo an epithelial-to-mesenchymal transition to give rise to neural crest (NC) cells with corresponding rostrocaudal identity.

2022-03-27 | GSE150709 | GEO

NEUROMESO

Project description:Exposure of mouse ESCs to a sequence of extrinsic signals, which recapitulates in vivo development, generates a bipotential neuromesodermal precursor (NMP) that can be directed to differentiate into either spinal cord or paraxial mesodermal tissue. To induce differentiation,mouse ES cells were plated on CellBINDSurface dishes (Corning) precoated with 0.1% gelatin (Sigma) at a density of 5x10^3 cells cm-2 in N2B27 medium. Cells were grown in N2B27 supplemented with 10ng/ml bFGF (R&D) for 3 days (D1-D3) and then were transferred into serum free media without bFGF (D3-D5). To induce ventral hindbrain identity NPCs (NH) 100nM RA (Sigma) and 500nM SAG (Calbiochem) was added from D3-D5. Spinal cord identity (NP) was induced by the addition of 5nM CHIR 99021 (Axon) from D2 to D3 followed by 100nM RA, 500nM SAG from D3-D5. To induce mesodermal differentiation the cells were treated with CHIR99021 from D2-D5.

2014-07-18 | E-MTAB-2268 | biostudies-arrayexpress

Step-wise differentiation of entire complement of spinal sensory interneurons from mouse embryonic stem cells (mESCs) using developmental logic [bulk RNA-seq]

Project description:We directed mESCs towards the neuromesodermal progenitor state (NMPs) that contribute to the spinal cord cells in the embryo. We then tested if ESC-derived NMPs can be directed to generate diverse sensory neuronal subtypes by testing different combinations of growth factors RA and BMP4 which are crucial for providing patterning information during spinal cord development. By bulk-RNA seq analysis of the entire timeline of the mESC differentiation under various conditions, we identified differentiation trajectories that lead to sensory neurons or completely different cardiac cell types under RA/+BMP4 conditions. We also characterized the gene expression changes that occur when cells transition from different states while differentiating into sensory neurons and identified Wnt signaling being a regulator of proliferation working directly downstream of BMP4 signaling in the mESC cultures.

2022-07-09 | GSE185889 | GEO

Neuromesodermal Progenitors are a Conserved Source of Spinal Cord with Divergent Growth Dynamics

Project description:Neuromesodermal Progenitors are a Conserved Source of Spinal Cord with Divergent Growth Dynamics

| PRJNA495749 | ENA

Gene expression in microdissected embryonic regions during mouse axis elongation.

Project description:This dataset contains spatiotemporal transcriptome information on different axial progenitors throughout mouse axis elongation. Neuromesodermal Progenitors (NMPs), Lateral and Paraxial Mesoderm Progenitors (LPMPs), and Notochord Progenitors (NotoPs) show distinct expression profiles. Extensive similarity exist between NMPs and their immediate mesoderm-committed descendants at each stage investigated. Over time transcriptional changes occur in LPMPs and NMPs, with the major change occurring in NMPs between early somitogenesis and completion of trunk morphogenesis. In contrast, NotoPs contain a more stable transcriptome over time.

2018-10-06 | GSE120870 | GEO

Generation of functional posterior spinal motor neurons from hPSCs-derived human spinal cord neural progenitor cells

Project description:Spinal motor neurons deficiency results in a series of devastating disorders such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA) and spinal cord injury (SCI). These devastating disorders are currently incurable, while human pluripotent stem cells (hPSCs) derived spinal motor neurons are promising but suffered by low-efficiency, functional immaturity and lacks of posterior cell identity. In this study, we have established human spinal cord neural progenitor cells (hSCNPCs) via hPSCs differentiated neuromesodermal progenitors (NMPs) and demonstrated the hSCNPCs can be continuously expanded up to 40 passages. hSCNPCs can be rapidly differentiated into posterior spinal motor neurons with high efficiency. The functional maturity has been examined in detail. Moreover, a co-culture scheme which is compatible for both neural and muscular differentiation is developed to mimic the neuromuscular junction (NMJ) formation in vitro. Together, these studies highlight the potential avenues for generating clinically relevant motor neurons and modelling neuromuscular diseases through our defined hSCNPCs.

2023-06-01 | GSE205718 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data