Poly-A RNA profiling of Drosophila neural stem cells (type I NBs) and GMCs of different ages reveal genes involved in cell fate stabilization
Ontology highlight
ABSTRACT:
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE104049 | GEO | 2018/06/27
REPOSITORIES: GEO
Similar Datasets
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.
This model is hosted on BioModels Database and identified by: BIOMD0000000396.
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 | BIOMD0000000396 | BioModels
Project description:Sivakumar2011_WntSignalingPathway
The secreted protein Wnt activates the
heptahelical receptor Frizzled on nieghboring cells. Activation of
Frizzled causes the recruitment of additional membrane proteins
which in turn result in 1) the activation of the protein
Dishevelled via phosphorylation and 2) the activation of a
heterotrimeric G protein of unknown type. Activation of Dishevelled
results in the down-regulation of the Beta-Catenin destruction
complex which causes ubiquitination of Beta-Catenin and its
ultimate degradation via the proteasome. Inhibition of the
Beta-Catenin destruction complex yields a higher cytosolic
concentration of Beta-Catenin, which enters the nucleus, binds
various transcriptional regulatory molecules including the TCF/LEF
class of proteins, and results in the transcription of TCF/LEF
target genes. Activation of the heterotrimeric G-protein pathway in
turn activates Phospholipase C which in turn catalyzes the
catalysis of PI(4,5)P2 into DAG and IP3.
Reference:
The Wnt
signalling pathway.
You Wnt
some, you lose some: oncogenes in the Wnt signaling
pathway.
Wnt
signaling pathway.
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:
BIOMD0000000397.
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 | BIOMD0000000397 | BioModels
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: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:Tissue stem cells divide asymmetrically to self-renew and generate differentiated progeny to maintain tissue homeostasis. Escargot (Esg) is a transcriptional repressor that is expressed in multiple stem cell populations in Drosophila melanogaster. Reduced esg function in intestinal stem cells (ISCs) causes a loss of ISCs and a biased differentiation of the daughter enteroblasts (EBs) toward the enteroendocrine (EE) cell fate. Loss of esg leads to an upregulation of differentiation factors and reduced Notch activity within EBs, indicating that Esg is a pivotal regulator of homeostasis in the intestine, supporting self-renewal to maintain a healthy stem cell pool as well as differentiation of progenitor cells. To identify potential transcriptional targets that mediate these phenotypes, in vivo DamID was used to generate the data deposited herein. 3 biological relicates were performed for Esg (with one dye-swap).
2014-11-18 | E-GEOD-55226 | biostudies-arrayexpress
Project description:Tissue stem cells divide asymmetrically to self-renew and generate differentiated progeny to maintain tissue homeostasis. Escargot (Esg) is a transcriptional repressor that is expressed in multiple stem cell populations in Drosophila melanogaster. Reduced esg function in intestinal stem cells (ISCs) causes a loss of ISCs and a biased differentiation of the daughter enteroblasts (EBs) toward the enteroendocrine (EE) cell fate. Loss of esg leads to an upregulation of differentiation factors and reduced Notch activity within EBs, indicating that Esg is a pivotal regulator of homeostasis in the intestine, supporting self-renewal to maintain a healthy stem cell pool as well as differentiation of progenitor cells. To identify potential transcriptional targets that mediate these phenotypes, in vivo DamID was used to generate the data deposited herein.
2014-11-18 | GSE55226 | GEO
Project description:Sivakumar2011 - Hedgehog Signaling Pathway
This is the current model for the Hedgehog signaling pathway. The best data for mechanism of signaling has been worked out in Drosophila, so this model is based largely on Drosophila data. Hedgehog target genes vary from tissue to tissue, so the identities of individual target genes have not been listed. The main difference between the Drosophila and mammalian Hedgehog signaling pathways is the fact that there are three mammalian homologs of Cubitus interruptus, Gli1 Gli2 and Gli3. Some or all of the mammalian homologs may be proteolytically processed, but the data are controversial. There are two mammalian Ptc genes and three mammalian Hedgehog genes as well. The pathway for Sonic Hedgehog appears to be most similar to the Drosophila hedgehog pathway.
References:
Hedgehog signaling in animal development: paradigms and principles.
Sonic hedgehog in the nervous system: functions, modifications and mechanisms.
Hedgehog signal transduction: recent findings.
Hedgehog signaling: Costal-2 bridges the transduction gap.
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: BIOMD0000000395.
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 | BIOMD0000000395 | BioModels
Project description:Mammalian SWI/SNF complexes are multi-subunit chromatin remodeling complexes associated with an ATPase, either SMARCA4 or SMARCA2. Heterozygous mutations in the SMARCA2 ATPase cause Nicolaides-Baraitser Syndrome (NCBRS), an intellectual disability syndrome associated with delayed speech onset. We engineered human embryonic stem cells (hESCs) to carry NCBRS-associated heterozygous SMARCA2 K755R or R1159Q mutations. While SMARCA2 mutant hESCs were phenotypically normal, differentiation to neural progenitors cells (NPCs) was severely impaired. We find that SMARCA2 mutations cause enhancer reorganization with loss of SOX3-dependent neural enhancers and prominent emergence of astrocyte-specific de novo enhancers. Changes in chromatin accessibility at enhancers were associated with an increase in SMARCA2 binding and retargeting of SMARCA4. We show that AP-1 family member FRA2 is aberrantly overexpressed in SMARCA2 mutant NPCs, where it functions as a pioneer factor at de novo enhancers. Together, our results demonstrate SMARCA2 mutations cause impaired differentiation through enhancer reprogramming via inappropriate targeting of SMARCA4.
2019-07-30 | GSE122631 | GEO
Project description:To identify Lgl binding proteins, we purified Lgl-containing protein complexes from cultured Drosophila S2 cells, using the single-step streptavidin purification from stable cell lines expressing SBP-tagged Lgl, followed by nanoLC-MS/MS analysis of the interactors. This study revealed the binding of Lgl to Vap33, which we further connected to the function of the vacuolar ATPase and regulation of Notch signaling.
2018-06-10 | PXD009568 | Pride
Project description:Decoding heterogeneity of pluripotent stem cell (PSC)-derived neural progeny is fundamental for revealing the origin of diverse progenitors, for defining their lineages, and for identifying fate determinants driving transition through distinct potencies. Here we prospectively isolated consecutively appearing PSC-derived primary progenitors based on their Notch activation state. We first isolate early neuroepithelial cells and show their broad Notch-dependent developmental and proliferative potential. Neuroepithelial cells further yield successive Notch-dependent functional primary progenitors, from early and mid neurogenic radial glia and their derived basal progenitors, to gliogenic radial glia and adult-like neural progenitors, together recapitulating hallmarks of neural stem cell (NSC) ontogeny. Gene expression profiling reveals dynamic stage specific transcriptional patterns that may link development of distinct progenitor identities through Notch activation. Our observations provide a platform for characterization and manipulation of distinct progenitor cell types amenable for developing streamlined neural lineage specification paradigms for modeling development in health and disease. Human embryonic stem cells (hESCs) H9 were differentiated into 5 distinct populations of neural precursor cells (NPCs) over a time course of 200 days. Each neural precursor populations was then sorted for HES5 expression based on a GFP-HES5 reporter. Both the HES5 positive and HES5 negative populations were then subjected to microarray profiling in singlicate, as well as the hESCs using GeneChipPrimeView Human Gene Expression Array
2015-02-18 | E-GEOD-65369 | biostudies-arrayexpress