Development of gene expression signatures for practical radiation biodosimetry
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE29093 | GEO | 2012/04/09
SECONDARY ACCESSION(S): PRJNA140319
REPOSITORIES: GEO
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Project description:Genome-wide analysis of miRNA expression was performed in Activin A and Wnt3a-treated mouse ESCs during the different stages of DE differentiation to identify candidate miRNAs likely to be involved in Wnt3a and Activin A induced DE formation. Our analysis exhibited a distinct miRNA expression finger print. Furthermore, we found that forced expression of a subset of synergistically regulated miRNAs could partially mimic the roles of Wnt3a and Activin A. Pathway analyses also revealed the involvement of histone acetylation in Activin A/Wnt3a-driven DE differentiation, which is further confirmed by treating the cells with small molecular weight HDAC inhibitors as well as ChIP experiments. Our study established a regulatory cascade from extracellular cytokine treatment to miRNA expression to histone modification in cell nucleus during DE differentiation. ESCs were treated with 100ng/ml Activin A, or 50ng/ml Wnt3a, or 100ng/ml Activin A plus 50ng/ml Wnt3a, and the samples were collected at 1 day, 3 days, and 5 days after treatment, respectively. Cells treated with the same medium without growth factors were used as the negative controls for each time point.
2012-04-08 | E-GEOD-29093 | biostudies-arrayexpress
Project description:The miRNAs play important roles in regulating gene expression at post-transcriptional level through fine-tuning of protein-encoding gene expression, and are involved in regulating important biological processes in different cells and tissue types, including osteoblast differentiation. Canonical Wnt signaling is also known to play pleiotropic roles in regulating cell differentiation during mammalian osteogenesis, although the role of miRNAs is not established for Wnt signaling in osteoblast differentiation. Here we examined the role of candidate miRNAs expressed differentially after Wnt3a expression during osteoblast differentiation. Overexpression of the Wnt3a gene resulted in increased transcription of the ALP gene, but in decreased transcription of the Runx2, Col1a and OCN genes in osteoblastic MC3T3-E1 cells. Analysis of miRNA expression profile showed that 14 miRNAs were up-regulated and 21 miRNAs were down-regulated after Wnt3a overexpression in MC3T3-E1 cells. TGF-beta3 is presumed to be a candidate target gene of one of the down-regulated miRNAs with database search. Transfection of the miRNA mimic into MC3T3-E1 cells significantly inhibited the TGF-beta3 mRNA level and resultant protein expression, although overexpression of the Wnt3a gene could reverse the effect of the miRNA, resulting in the increased TGF-beta3 mRNA and protein levels. These results suggest that the miRNA is involved in osteoblast differentiation as a critical regulatory factor, mediating crosstalk between Wnt3a signaling pathway and TGF-beta3 signaling pathway.
2018-03-20 | GSE96757 | GEO
Project description:The Wnt3a/?-catenin and Activin/Smad2,3 signaling pathways synergize to induce endodermal differentiation of human embryonic stem cells, however the mechanism is not well-understood. Using ChIP-seq and GRO-seq analyses, we report here that hESC enhancers, including Wnt3a/LEF-1 sites, hold enhancer RNAPII complexes (eRNAPII) containing high levels of Ser5P and low Ser7P. In Wnt3a signaling, ?-catenin recruits cohesin to the LEF-1:eRNAPII sites to induce enhancer-promoter looping and activate transcription of mesoendodermal (ME) genes. However, paused Ser5P-RNAPII complexes accumulate at these genes, indicating that elongation remains limiting. Subsequent Activin/Smad2,3 signaling increases P-TEFb occupancy, CTD-Ser7P, and productive elongation at ME genes. Additionally, ME genes, including EOMES and MIXL1, are repressed by the Hippo regulator, Yap1, an essential pluripotency factor. GRO-seq experiments indicate that Yap1 blocks nascent transcription and controls NELF occupancy on ME genes. Thus, Wnt3a/?-catenin and Activin/Smad2,3 pathways up-regulate transcription initiation and elongation, respectively, to overcome Yap1 repression during early hESC differentiation ChIP-seq and GROseq experiments in H1 hESCs. Cells were treated with Wnt3a (200ng/ml), Activin A (100ng/ml) or Wnt3a+Activin A (W200ng/ml+A100ng/ml) for 4h (ChIP-seq) or 6h (GRO-seq). GRO-seq in YAP depleted cells were carried out following transfection with control or YAP siRNAs . After 48h transfection, cells were left untreated or treated with Wnt3a+Activin (W200ng/ml+A100ng/ml) for additional 6h.
2015-05-04 | E-GEOD-64758 | biostudies-arrayexpress
Project description:The Wnt3a/β-catenin and Activin/Smad2,3 signaling pathways synergize to induce endodermal differentiation of human embryonic stem cells, however the mechanism is not well-understood. Using ChIP-seq and GRO-seq analyses, we report here that hESC enhancers, including Wnt3a/LEF-1 sites, hold enhancer RNAPII complexes (eRNAPII) containing high levels of Ser5P and low Ser7P. In Wnt3a signaling, β-catenin recruits cohesin to the LEF-1:eRNAPII sites to induce enhancer-promoter looping and activate transcription of mesoendodermal (ME) genes. However, paused Ser5P-RNAPII complexes accumulate at these genes, indicating that elongation remains limiting. Subsequent Activin/Smad2,3 signaling increases P-TEFb occupancy, CTD-Ser7P, and productive elongation at ME genes. Additionally, ME genes, including EOMES and MIXL1, are repressed by the Hippo regulator, Yap1, an essential pluripotency factor. GRO-seq experiments indicate that Yap1 blocks nascent transcription and controls NELF occupancy on ME genes. Thus, Wnt3a/β-catenin and Activin/Smad2,3 pathways up-regulate transcription initiation and elongation, respectively, to overcome Yap1 repression during early hESC differentiation
2015-05-04 | GSE64758 | GEO
Project description:Pluripotent hESCs can differentiate into the three primary embryonic lineages (endoderm, mesoderm, ectoderm) as well as extraembryonic tissues. Definitive endoderm (DE) is the first step into the pathway to endoderm dreived tissues (pancreas, liver, gut, lung). We used microarrays to detail the changes in microRNA expression during the transition from pluripotent hESCs into definitive endoderm. hESCs (H9) were differentiated in the presence of Activin A and Wnt3A under low serum conditions to induce DE formation. Samples were collected at day 0 (hESCs), and day 4 (DE).
2010-07-30 | E-GEOD-16689 | biostudies-arrayexpress
Project description:To further development of our gene expression approach to biodosimetry, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to distinguish radiation dose across an exposure range relevant for medical decision-making in a radiological emergency. Human peripheral blood from healthy donors was irradiated ex vivo, and a 74-gene consensus signature was identified that distinguished between four radiation doses (0.5, 2, 5 and 8 Gy) and control samples. The same set of genes separated samples by exposure level at both six and 24 hours after treatment, with overlap evident only at the highest two doses (5 and 8 Gy). Expression of five genes (CDKN1A, FDXR, SESN1, BBC3 and PHPT1) from this signature was quantified in the same RNA samples by real-time PCR, confirming low variability between donors as well as the predicted radiation response pattern. Keywords: Dose Response, stress response, radiation response, biodosimetry
2008-07-01 | GSE8917 | GEO
Project description:hESCs can differentiate into the three primary embryonic lineages (endoderm, mesoderm, ectoderm) as well as extraembryonic tissues. Definitive endoderm (DE) is the first step into the pathway to endoderm derived tissues: pancreas, liver, gut, lung. We used microarrays to detail the changes in mRNA expression during the transition from pluripotent hESCs into definitive endoderm. hESCs (Cyt49) were differentiated in the presence of Activin A and Wnt3A under low serum conditions to induce DE formation. Samples were collected at day 0, day 2 and day 4.
2010-07-30 | E-GEOD-16681 | biostudies-arrayexpress
Project description:Pluripotent hESCs can differentiate into the three primary embryonic lineages (endoderm, mesoderm, ectoderm) as well as extraembryonic tissues. Definitive endoderm is the first step into the pathway to endoderm dreived tissues (pancreas, liver, gut, lung) We used microarrays to detail the changes in microRNA expression during the transition from pluripotent hESCs into definitive endoderm hESCs (Cyt49) were differentiated in the presence of Activin A and Wnt3A under low serum conditions to induce DE. formation. Samples were collected at day 0 (hESCs), and day 4 (DE).
2010-07-30 | E-GEOD-16687 | biostudies-arrayexpress
Project description:Proctor2017 - Identifying microRNA for muscle regeneration during ageing (Mir1_in_muscle)
This model is described in the article:
Using computer simulation
models to investigate the most promising microRNAs to improve
muscle regeneration during ageing
Carole J. Proctor & Katarzyna
Goljanek-Whysall
Nature Scientific Reports
Abstract:
MicroRNAs (miRNAs) regulate gene expression through
interactions with target sites within mRNAs, leading to
enhanced degradation of the mRNA or inhibition of translation.
Skeletal muscle expresses many different miRNAs with important
roles in adulthood myogenesis (regeneration) and myofibre
hypertrophy and atrophy, processes associated with muscle
ageing. However, the large number of miRNAs and their targets
mean that a complex network of pathways exists, making it
difficult to predict the effect of selected miRNAs on
age-related muscle wasting. Computational modelling has the
potential to aid this process as it is possible to combine
models of individual miRNA:target interactions to form an
integrated network. As yet, no models of these interactions in
muscle exist. We created the first model of miRNA:target
interactions in myogenesis based on experimental evidence of
individual miRNAs which were next validated and used to make
testable predictions. Our model confirms that miRNAs regulate
key interactions during myogenesis and can act by promoting the
switch between quiescent/proliferating/differentiating
myoblasts and by maintaining the differentiation process. We
propose that a threshold level of miR-1 acts in the initial
switch to differentiation, with miR-181 keeping the switch on
and miR-378 maintaining the differentiation and miR-143
inhibiting myogenesis.
This model is hosted on
BioModels Database
and identified by:
MODEL1704110000.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
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.
2017-09-26 | MODEL1704110000 | BioModels
Project description:Proctor2017 - Identifying microRNA for muscle regeneration during ageing (Mir378_in_muscle)
This model is described in the article:
Using computer simulation
models to investigate the most promising microRNAs to improve
muscle regeneration during ageing
Carole J. Proctor & Katarzyna
Goljanek-Whysall
Scientific Reports
Abstract:
MicroRNAs (miRNAs) regulate gene expression through
interactions with target sites within mRNAs, leading to
enhanced degradation of the mRNA or inhibition of translation.
Skeletal muscle expresses many different miRNAs with important
roles in adulthood myogenesis (regeneration) and myofibre
hypertrophy and atrophy, processes associated with muscle
ageing. However, the large number of miRNAs and their targets
mean that a complex network of pathways exists, making it
difficult to predict the effect of selected miRNAs on
age-related muscle wasting. Computational modelling has the
potential to aid this process as it is possible to combine
models of individual miRNA:target interactions to form an
integrated network. As yet, no models of these interactions in
muscle exist. We created the first model of miRNA:target
interactions in myogenesis based on experimental evidence of
individual miRNAs which were next validated and used to make
testable predictions. Our model confirms that miRNAs regulate
key interactions during myogenesis and can act by promoting the
switch between quiescent/proliferating/differentiating
myoblasts and by maintaining the differentiation process. We
propose that a threshold level of miR-1 acts in the initial
switch to differentiation, with miR-181 keeping the switch on
and miR-378 maintaining the differentiation and miR-143
inhibiting myogenesis.
This model is hosted on
BioModels Database
and identified by:
MODEL1704110002.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
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.
2017-09-26 | MODEL1704110002 | BioModels