Ontology highlight
ABSTRACT:
PROVIDER: PRJNA961204 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24291600_1.fastq.gz | Fastqsanger.gz | |||
| SRR24291600_2.fastq.gz | Fastqsanger.gz | |||
| SRR24291601_1.fastq.gz | Fastqsanger.gz | |||
| SRR24291601_2.fastq.gz | Fastqsanger.gz | |||
| SRR24291602_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 72 |
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Project description:Adult Neural Stem Cells (aNSCs) in the ventricular-subventricular zone (V-SVZ) are largely quiescent. Here, we characterize the mechanism underlying the functional role of a cell-signalling inhibitory protein, LRIG1, in the control of aNSCs proliferation. Using constitutive Lrig1 knockout models, we show that Lrig1 ablation results in increased aNSCs proliferation with no change in neuronal progeny and that this hyperproliferation likely does not result from activation of the epidermal growth factor receptor (EGFR). Loss of LRIG1, however, does lead to impaired activation of canonical transforming growth factor beta (TGFβ) and bone morphogenic protein (BMP) signalling pathways. Biochemically, we show in vitro that LRIG1 is able to bind TGFβ/BMP receptors and the TGFβ1 ligand. Finally, we show that the consequences of these interactions are to facilitate SMAD phosphorylation and pathway activation. Collectively, these data suggest that, unlike in embryonic neural stem cells where EGFR is the primary mechanism of action, LRIG1 and TGFβ pathways positively work together to fulfill their inhibitory roles in aNSCs.
2024-07-08 | GSE263575 | GEO
Project description:Sivakumar2011 - EGF Receptor Signaling Pathway
EGFR belongs to the human epidermal receptor (HER) family of receptor tyrosine kinases, which consists of four closely related receptors (EGFR (HER1, erbB1), HER2 (neu, erbB2), HER3 (erbB3), and HER4 (erbB4)) that mediate cellular signaling pathways involved in growth and proliferation in response to the binding of a variety of growth factor ligands. There are currently six known endogenous ligands for EGFR: EGF, transforming growth factor- (TGF-), amphiregulin, betacellulin, heparin-binding EGF (HB-EGF), and epiregulin.Upon ligand binding, the EGFR forms homo- or heterodimeric complexes (usually with HER2), which leads to activation of the receptor tyrosine kinase, via autophosphorylation.
References:
The EGF receptor family--multiple roles in proliferation, differentiation, and neoplasia with an emphasis on HER4.
An open-and-shut case? Recent insights into the activation of EGF/ErbB receptors.
EGF receptor signaling: putting a new spin on eye development.
Epidermal growth factor receptor: a promising target in solid tumours.
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.
This model is hosted on BioModels Database and identified by: BIOMD0000000394.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000394 | BioModels
Project description:The hair follicle stem cell niche is an immune-privileged microenvironment, characterized by reduced antigen presentation, thus shielding against permanent immune-mediated tissue damage. In this study, we demonstrated the protective role of hair follicle-specific epidermal growth factor receptor (EGFR) against scarring hair follicle destruction. Mechanistically, disruption of EGFR signalling generated a cell-intrinsic hypersensitivity within the JAK-STAT1 pathway, which, synergistically with interferon gamma expressing CD8 T-cell and NK-cell-mediated inflammation, compromised the stem cell niche. Hair follicle-specific genetic depletion of either JAK1/2 or STAT1 or therapeutic inhibition of JAK1/2 ameliorated the inflammation, restored skin barrier function and activated the residual stem cells to resume hair growth in mouse models of epidermal and hair follicle-specific EGFR deletion. Skin biopsies from EGFR inhibitor-treated and cicatricial alopecia patients indicated active STAT1 signalling and interferon target expression. Notably, a case study of folliculitis decalvans, characterized by progressive hair loss, scaling and perifollicular erythema, demonstrated successful treatment with JAK1/2 inhibition. Our findings offer molecular insights and present a mechanism-based therapeutic strategy for addressing chronic folliculitis associated with EGFR-inhibitor anti-cancer therapy and cicatricial alopecia.
2024-07-31 | GSE273571 | GEO
Project description:The hair follicle stem cell niche is an immune-privileged microenvironment, characterized by reduced antigen presentation, thus shielding against permanent immune-mediated tissue damage. In this study, we demonstrated the protective role of hair follicle-specific epidermal growth factor receptor (EGFR) against scarring hair follicle destruction. Mechanistically, disruption of EGFR signalling generated a cell-intrinsic hypersensitivity within the JAK-STAT1 pathway, which, synergistically with interferon gamma expressing CD8 T-cell and NK-cell-mediated inflammation, compromised the stem cell niche. Hair follicle-specific genetic depletion of either JAK1/2 or STAT1 or therapeutic inhibition of JAK1/2 ameliorated the inflammation, restored skin barrier function and activated the residual stem cells to resume hair growth in mouse models of epidermal and hair follicle-specific EGFR deletion. Skin biopsies from EGFR inhibitor-treated and cicatricial alopecia patients indicated active STAT1 signalling and interferon target expression. Notably, a case study of folliculitis decalvans, characterized by progressive hair loss, scaling and perifollicular erythema, demonstrated successful treatment with JAK1/2 inhibition. Our findings offer molecular insights and present a mechanism-based therapeutic strategy for addressing chronic folliculitis associated with EGFR-inhibitor anti-cancer therapy and cicatricial alopecia.
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Project description:The prion protein (PrP) evolved from the subbranch of ZIP metal ion transporters comprising ZIPs 5, 6 and 10, raising the prospect that the study of these ZIPs may reveal insights relevant for understanding PrP function. PrP and ZIP6 are required for the execution of a cellular program known as epithelial-to-mesenchymal transition (EMT). Polysialylation of neural cell adhesion molecule 1 (NCAM1) during EMT is also controlled by PrP. Here we report the ZIP6 interactome and ZIP6-dependent NCAM1 interactome in a mouse cell EMT model.
2017-02-13 | PXD004685 | Pride
Project description:Sivakumar2011_NeuralStemCellDifferentiation_Crosstalk
This model is generated by integrating
BIOMD0000000394
(EGFR),
BIOMD0000000395
(Hedgehog),
BIOMD0000000396
(Notch) and
BIOMD0000000397
(Wnt), to investigate the signalling crosstalk between the four
pathways.
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 2011 Oct; 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.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000398.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000398 | BioModels
Project description:Adult stem cells (SCs) are essential for tissue maintenance and regeneration yet are susceptible to SC senescence during aging. Here we demonstrate the importance of cellular NAD+ level and its impact on mitochondrial activity as a pivotal switch to modulate muscle stem cell (MuSC) senescence. Importantly, the induction of the mitochondrial unfolded protein response (UPRmt) and of prohibitin proteins, subsequent to increasing cellular NAD+ with the precursor nicotinamide riboside (NR), rejuvenates MuSCs in aged mice. NR also prevents MuSCs senescence in Mdx mice, a mouse model of muscular dystrophy. Extending these observations to other SC pools and on the organism as a whole, we demonstrate that NR delays neural stem cell (NSC) and melanocyte stem cell (McSC) senescence, while also increasing mouse lifespan. Strategies that conserve cellular NAD+ could therefore be utilized to reprogram dysfunctional SCs in aging and disease to improve lifespan in mammals
2022-02-22 | PXD003865 | Pride
Project description:Activating mutations in the epidermal growth factor receptor (EGFR) are common driver mutations in non-small cell lung cancer (NSCLC). First, second and third generation EGFR tyrosine kinase inhibitors (TKIs) are effective at inhibiting mutant EGFR NSCLC, however, acquired resistance is a major issue, leading to disease relapse. Here, we characterize a small molecule, EMI66, an analog of a small molecule which we previously identified to inhibit mutant EGFR signalling via a novel mechanism of action. We show that EMI66 attenuates receptor tyrosine kinase (RTK) expression and signalling and alters the electrophoretic mobility of Coatomer Protein Complex Beta 2 (COPB2) protein in mutant EGFR NSCLC cells. Moreover, we demonstrate that EMI66 can alter the subcellular localization of EGFR and COPB2 within the early secretory pathway. Furthermore, we find that COPB2 knockdown reduces the growth of mutant EGFR lung cancer cells, alters the post-translational processing of RTKs, and alters the endoplasmic reticulum (ER) stress response pathway. Lastly, we show that EMI66 treatment also alters the ER stress response pathway and inhibits the growth of mutant EGFR lung cancer cells and organoids. Our results demonstrate that targeting of COPB2 with EMI66 presents a viable approach to attenuate mutant EGFR signalling and growth in NSCLC.
2024-06-05 | GSE178289 | GEO
Project description:Acting downstream of many growth factors, extracellular signal-regulated kinase (ERK) plays a pivotal role in regulating cell proliferation and tumorigenesis, where its spatiotemporal dynamics, as well as its strength, determine cellular responses. Here, we uncover the ERK activity dynamics in intestinal epithelial cells (IECs) and their association with tumour characteristics. In vivo imaging identified two distinct modes of ERK activity, sustained and pulse-like activity, in IECs. The sustained and pulse-like activity depended on ErbB2 and EGFR, respectively. Notably, deregulated activation of Wnt signalling, the earliest event in intestinal tumorigenesis, augmented EGFR signalling and exalted it to a dominant driver of ERK activity dynamics, which rendered IECs addicted to EGFR signalling. Furthermore, the frequency of ERK activity pulses was also increased to promote cell proliferation. Thus, ERK activity dynamics are defined by composite inputs from EGFR and ErbB2 signalling in IECs and their alterations underlie tumour-specific sensitivity to pharmacological EGFR inhibition. In this microarray analysis, we aimed to elucidate molecular mechanisms that mediate Wnt signalling activation-induced alterations in EGFR-ERK signalling dynamics.
2018-02-08 | GSE110257 | GEO