Barcoding Notch signaling in the developing brain
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1116548 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29181700.fastq.gz | Fastqsanger.gz | |||
| SRR29181701_1.fastq.gz | Fastqsanger.gz | |||
| SRR29181701_2.fastq.gz | Fastqsanger.gz | |||
| SRR29181702.fastq.gz | Fastqsanger.gz | |||
| SRR29181703.fastq.gz | Fastqsanger.gz |
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Project description:Developmental signaling inputs are fundamental for shaping cell fates and behavior. However, traditional fluorescent-based signaling reporters have limitations in scalability and molecular resolution of cell types. We present SABER-seq, a CRISPR-Cas molecular recorder that stores transient developmental signaling cues as permanent mutations in cellular genomes for deconstruction at later stages via single-cell transcriptomics. We applied SABER-seq to record Notch signaling in developing zebrafish brains. SABER-seq has two components: a signaling sensor and a barcode recorder. The sensor activates Cas9 in a Notch-dependent manner with inducible control while the recorder obtains mutations in ancestral cells where Notch is active. We combine SABER-seq with an expanded juvenile brain atlas to identify cell types derived from Notch-active founders. Our data reveals rare examples where differential Notch activity in ancestral progenitors is detected in terminally differentiated neuronal subtypes. SABER-seq is a novel platform for rapid, scalable and high-resolution mapping of signaling activity during development.
2024-12-11 | GSE268356 | GEO
Project description:Sivakumar2011 - Notch Signaling Pathway
Notch is a transmembrane receptor that mediates local cell-cell communication and coordinates a signaling cascade. It plays a key role in modulating cell fate decisions throughout the development of invertebrate and vertebrate species and the misregulation leads to a number of human diseases.
References:
Notch signaling: from the outside in.
Notch signaling in hematopoiesis and early lymphocyte development.
An overview of the Notch signalling pathway.
Notch and cancer: best to avoid the ups and downs.
Notch signaling: control of cell communication and cell fate.
This model is described in the article:
A systems biology approach to model neural stem cell regulation by notch, shh, wnt, and EGF signaling pathways.
Sivakumar KC, Dhanesh SB, Shobana S, James J, Mundayoor S.
Omics: a Journal of Integrative Biology. 2011; 15(10):729-737
Abstract:
The Notch, Sonic Hedgehog (Shh), Wnt, and EGF pathways have long been known to influence cell fate specification in the developing nervous system. Here we attempted to evaluate the contemporary knowledge about neural stem cell differentiation promoted by various drug-based regulations through a systems biology approach. Our model showed the phenomenon of DAPT-mediated antagonism of Enhancer of split [E(spl)] genes and enhancement of Shh target genes by a SAG agonist that were effectively demonstrated computationally and were consistent with experimental studies. However, in the case of model simulation of Wnt and EGF pathways, the model network did not supply any concurrent results with experimental data despite the fact that drugs were added at the appropriate positions. This paves insight into the potential of crosstalks between pathways considered in our study. Therefore, we manually developed a map of signaling crosstalk, which included the species connected by representatives from Notch, Shh, Wnt, and EGF pathways and highlighted the regulation of a single target gene, Hes-1, based on drug-induced simulations. These simulations provided results that matched with experimental studies. Therefore, these signaling crosstalk models complement as a tool toward the discovery of novel regulatory processes involved in neural stem cell maintenance, proliferation, and differentiation during mammalian central nervous system development. To our knowledge, this is the first report of a simple crosstalk map that highlights the differential regulation of neural stem cell differentiation and underscores the flow of positive and negative regulatory signals modulated by drugs.
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2024-09-02 | BIOMD0000000396 | BioModels
Project description:Comprehensive spatiotemporal mapping of single-cell lineages in developing mouse brain by CRISPR-based barcoding
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Project description:Single cell profiling of the developing mouse brain and spinal cord with split-pool barcoding
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Project description:Maternal antibodies specific for antigens in the developing brain are implicated as risk factors for neurodevelopmental disorders, but how these antibodies interfere with neurodevelopment remain speculative. It has been postulated that immunoglobulin G-immune complexes (IgG-IC) activate Fc gamma receptors (FcγR) on non-immune cells in the brain, thereby modulating intracellular signaling and/or internalizing function-blocking antibodies specific for intracellular antigens. However, testing this hypothesis has been hindered by the paucity of data regarding FcγR in the developing brain. Thus, we first investigated FcγR expression in the brain of neonatal male and female rats using quantitative PCR analyses. FcgrIa, FcgrIIa, FcgrIIb, FcgrIIIa and Fcgrt transcripts were detectable in the cortex, hippocampus and cerebellum at postnatal days 1 and 7. These transcripts were also present in primary hippocampal and cortical cell cultures, where their expression was upregulated by IFNγ. In order to confirm protein abundance of FcγRIa, FcγRIIb and FcγRIIIa in cultured hippocampal and cortical neurons and astrocytes on the single cell and tissue level we used immunocytochemistry, western blotting, proteotype analysis, and flow cytometry. The data shows that a subpopulation of these cells co-express the excitatory FcγRIa and the inhibitory FcγRIIb. Functional analysis shows that exposure of hippocampal and cortical cell cultures to IgG-IC increased intracellular calcium and Erk phosphorylation, and triggered FcγR-mediated internalization of IgG. Collectively, these data demonstrate that developing neurons and astrocytes express signaling competent FcγR. which could establish a molecular mode of action of maternal antibodies could influence vulnerability to neurodevelopmental disorders via direct interactions with FcγR on non-immune cells in the developing brain. These findings support the hypothesis that maternal antibodies influence vulnerability to neurodevelopmental disorders via direct interactions with FcγR on non-immune cells in the developing brain.
2018-01-11 | PXD006904 | Pride
Project description:Using a hitherto uncharacterized knockout mouse model of Notch 3, a Notch signaling receptor paralogue highly expressed in vascular SMCs, we uncover a striking susceptibility to ischemic stroke upon challenge. Cellular and molecular analyses of vascular SMCs derived from these animals associate Notch 3 activity to the expression of specific gene targets, whereas genetic rescue experiments unambiguously link Notch 3 function in vessels to the ischemic phenotype. Microarray Studies. Biotinylated cRNA samples from freshly sorted brain SMCs (four Notch 3 +/- mice and five Notch 3 -/- mice) were fragmented before hybridization (15 ug each) onto mouse 430 2.0 Affymetrix chips. The chips were washed, stained by using strepavidin-phycoerytrin, and scanned the next day as described in ref. 24. For data normalization, all probe sets were scaled to a target intensity of 150. Microarray data analysis was performed by using Rosetta Resolver. All cells were from 10- to 12-week-old male mice. Gene Ontology Analyses. PANTHER software was used to define over- and underrepresented functions in the list of signature genes found by microarray analysis (25). P values were calculated by using binomial statistics.
2014-06-11 | E-GEOD-58368 | biostudies-arrayexpress
Project description:Loss or damage to the mandible due to trauma, treatment of oral malignancies, and other diseases is currently treated using bone grafting techniques that suffer from numerous shortcomings and contraindications. Zebrafish naturally heal large injuries to their mandibular bone, and thus offer an opportunity to understand how to boost intrinsic healing ability. Using a novel her6:mCherry Notch reporter, we show that canonical Notch signaling is induced during the initial stages of cartilage callus formation in both mesenchymal cells and chondrocytes. We also show that modulation of Notch signaling during the initial postoperative period results in lasting changes to regenerate bone quantity one month later. Notch signaling is required for mandibular bone healing, as pharmacological inhibition of Notch signaling blocks cartilage callus formation and results in non-union. Conversely, conditional transgenic activation of Notch signaling accelerates regenerative ossification. Mechanistically, we report that postoperative Notch signaling regulates multiple phases of chondroid regeneration and patterns callus metabolic landscape. Given conserved functions of Notch signaling in bone repair across vertebrates, we propose that targeted activation of Notch signaling during the early phases of bone healing may have therapeutic value.
2022-03-07 | PXD027280 | Pride
Project description:Evolutionary changes in vertebrates are linked to genetic alterations that often affect tooth-crown shape, which is a criterion of speciation events, especially in mammals. The Notch pathway is highly conserved between species and controls morphogenetic processes in most developing organs, including teeth. Epithelial loss of the Notch-ligand Jagged1 in developing mouse molars affects the location, size and interconnections of their cusps that lead to minor tooth-crown shape modifications convergent to those observed along Muridae evolution. RNA sequencing analysis revealed that these alterations are due to the modulation of more than 2000 genes and that Notch signaling is a hub for significant morphogenetic networks, such as Wnts and Fibroblast Growth Factors. The modeling of these tooth-crown changes in mutant mice, via a three-dimensional metamorphosis approach, allowed prediction of how Jagged1-associated mutations in humans could affect the morphology of their teeth. These results shed new light on Notch/Jagged1-mediated signaling as one of the crucial components for dental variations in evolution.
2023-03-17 | GSE198920 | GEO
Project description:The Notch signaling pathway regulates fate decision, proliferation and differentiation of intestinal epithelial cells. However, the role of Notch signaling in colorectal cancer progression is largely unknown. Here we show that Notch signaling suppresses the progression of colorectal tumorigenesis, even though it augments tumor initiation. In contrast to adenomas of Apcmin mice, Notch-inactivated Apcmin adenomas showed more malignant characteristics, such as submucosal invasion and loss of glandular pattern. Conversely, Notch-activated Apcmin adenomas showed a reversion from high-grade to low-grade features, such as the restoration of adherent junctions. Expression profiling revealed that Notch signaling promotes the differentiation of tumor cells with down regulation of Wnt/beta-catenin target genes and inhibition of epithelial-mesenchymal transition. Comparison of mouse and human expression profiles also suggests the common role of Notch in inhibition of tumor progression. Interestingly, Notch signaling suppressed the expression of beta-catenin responsive genes through chromatin modification of Tcf4/beta-catenin binding sides. Our results suggest that Notch signaling has dual roles in colorectal tumorigenesis: promoting adenoma initiation, while inhibiting tumor progression to colorectal cancer. mRNAs from normal (WT, Notch-activated and Notch-inactivated) and tumor (WT, Notch-activated and Notch-inactivated) tissues were profiled.
2011-04-19 | E-GEOD-21392 | biostudies-arrayexpress
Project description:RNA-seq of Notch signaling responsive
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