Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA307115 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3057583.fastq.gz | Fastqsanger.gz | |||
| SRR3057584.fastq.gz | Fastqsanger.gz | |||
| SRR3057585.fastq.gz | Fastqsanger.gz | |||
| SRR3057586.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 4 of 4 |
Similar Datasets
Project description:The transforming growth factor beta (TGF-β) superfamily proteins are potent regulators of cellular development and differentiation. Long non-coding RNAs (lncRNAs) play widespread roles in spatial-temporal regulation of early development. However, the roles of lncRNAs regulated by nodal/TGF-β signaling is still elusive. Here, we showed a nodal-driven Smad induced lncRNA in mouse embryonic stem cells (mESCs), lncRNA-Smad7, which is divergently transcribed to Smad7, regulates cell fate determination through repressing Bmp2. Depletion of lncRNA-Smad7 dramatically impairs cardiomyocyte differentiation in mESCs. Moreover, LncRNA-Smad7 represses Bmp2 expression and binds at the promoter region of Bmp2. Importantly, knock-down Bmp2 rescues the defect of cardiomyocyte differentiation. Hence, we showed that lncRNA-Smad7 is antagonistic to BMP signaling in mESCs. Furthermore, lncRNA-Smad7 regulates cell fate determination between osteocytes and myocytes formation in C2C12 cells by repressing Bmp2. Thus, we provide new insights regarding the antagonistic effects between nodal/TGF-β and BMP signaling via lncRNA-Smad7.
2022-10-19 | GSE178136 | GEO
Project description:This model is from the article:
Quantitative analysis of transient and sustained transforming growth factor-β signaling dynamics.
Zhike Zi, Zipei Feng, Douglas A Chapnick, Markus Dahl, Difan Deng, Edda Klipp, Aristidis Moustakas & Xuedong Liu Molecular Systems Biology
2011 May 24;7:492. 21613981
,
Abstract:
Mammalian cells can decode the concentration of extracellular transforming growth factor-β (TGF-β) and transduce this cue into appropriate cell fate decisions. How variable TGF-β ligand doses quantitatively control intracellular signaling dynamics and how continuous ligand doses are translated into discontinuous cellular fate decisions remain poorly understood. Using a combined experimental and mathematical modeling approach, we discovered that cells respond differently to continuous and pulsating TGF-β stimulation. The TGF-β pathway elicits a transient signaling response to a single pulse of TGF-β stimulation, whereas it is capable of integrating repeated pulses of ligand stimulation at short time interval, resulting in sustained phospho-Smad2 and transcriptional responses. Additionally, the TGF-β pathway displays different sensitivities to ligand doses at different time scales. While ligand-induced short-term Smad2 phosphorylation is graded, long-term Smad2 phosphorylation is switch-like to a small change in TGF-β levels. Correspondingly, the short-term Smad7 gene expression is graded, while long-term PAI-1 gene expression is switch-like, as is the long-term growth inhibitory response. Our results suggest that long-term switch-like signaling responses in the TGF-β pathway might be critical for cell fate determination.
Note:
Developer of the model: Zhike Zi
Reference: Zi Z. et al., Quantitative Analysis of Transient and Sustained Transforming Growth Factor-beta Signaling Dynamics, Molecular Systems Biology, 2011
1. The global parameter that set the type of stimulation
(a) for sustained TGF-beta stimulation: set stimulation_type = 1.
(b) for single pulse of TGF-beta stimulation: set stimulation_type = 2.
parameter "single_pulse_duration" is for the duration of stimulation, for example,
single_pulse_duration = 0.5, for 0.5 min (30 seconds) of TGF-beta stimulation.
*Note: make sure that the time course cover the time point when the event is triggered.
(c) for single pulse of TGF-beta stimulation in COPASI
change the trigger of event "single_pulse_TGF_beta_washout"
from
"and(eq(stimulation_type, 2), eq(time, single_pulse_duration))" (for SBML-SAT)
to
"and(eq(stimulation_type, 2), gt(time, single_pulse_duration))" (for COPASI)
2. Notes for TGF-beta dose in terms of molecules per cell
(a) The following equation applies for conversion of TGF-beta dose in molecules per cell
TGF_beta_dose_mol_per_cell = initial TGF_beta_ex*1e-9*Vmed*6e23
(b) for standard experimental setup 1e6 cells in 2 mL medium
0.001 nM initial TGF_beta_ex is approximately equal to the dose of 1200 TGF-beta molecules/cell
0.050 nM initial TGF_beta_ex is approximately equal to the dose of 60000 TGF-beta molecules/cell
(c) For 1e6 cells in 10 mL medium, please change the initial compartment size of Vmed and the corresponding assignment rule for Vmed.
initial Vmed = 1e-8 (1e6 cells in 10 mL medium)
Vmed = 0.010/(1e6*exp(log(1.45)*time/1440)) (1e6 cells in 10 mL medium)
3. Please note that this model contains events and the medium compartment size is varied.
4. For the model simulation in SBML-SAT, please remove initialAssignments and save it as SBML Level 2 Verion 1 file.
2024-09-02 | BIOMD0000000342 | BioModels
Project description:Upon antigen recognition, CD8+ T cells undergo a robust expansion and differentiation to give rise to effector and memory CD8+ T cells. The spatial determinants for effector and memory CD8+ T cell fate decision during acute infection is poorly understood. By integrating single-cell RNA sequencing (scRNA-seq) and spatial resolved transcriptomics, we investigated the anatomical locations, cell-cell interactions and molecular mechanisms that contribute to memory CD8+ T cell differentiation. We found naïve CD8+ T cells adopted a divergent differentiation trajectory where they rapidly differentiated into memory precursors (MP) and IFN-responsive cells which represent the entry point of effector T cell lineage.In the spleen, monocytes were largely colocalized with CD8+ MP cells in an antigen stimulation-dependent manner. CD8+ T cells primed with monocytes, compared to DC populations, had significantly increased memory T cell differentiation. Mechanistically, monocytes promoted memory CD8+ T cell differentiation by providing TGF-β signaling. Our study reveals a novel spatial mechanism for memory CD8+ T cell fate decision, shedding lights on the importance of monocytes and TGF-β in fostering memory CD8+ T cell development.
2025-06-05 | GSE266606 | GEO
Project description:Retinoic acid (RA) is a central developmental signal whose perturbation results in teratogenic outcomes. RA are tightly regulated during early embryonic development to achieve fine-tuning of the instructive and permissive signals regulating multiple developmental processes including head formation. We aim to identify the key mechanisms underlying the homeostatic regulation and tuning of the retinoic acid signaling levels, the disruption of which in the head lead to wide ranging developmental malformations including microcephaly and other craniofacial defects. We performed transient physiological RA signaling disturbances during Xenopus laevis embryogenesis followed by kinetic RNAseq analysis of the recovery at multiple time points.
2021-09-29 | GSE154399 | GEO
Project description:Retinoic acid (RA) is a central developmental signal whose perturbation results in teratogenic outcomes. RA is tightly regulated during early embryonic development to achieve fine-tuning of the instructive and permissive signals regulating multiple developmental processes including head formation. We aim to identify the key mechanisms underlying the homeostatic regulation and tuning of the retinoic acid signaling levels, the disruption of which in the head lead to wide ranging developmental malformations including microcephaly and other craniofacial defects. We performed transient physiological RA signaling disturbances during Xenopus laevis embryogenesis followed by kinetic gene expression analysis of the recovery at multiple time points.
2021-09-29 | GSE154407 | GEO
Project description:Recently, microRNAs (miRNAs) have emerged as new players in the fine tuning of embryo development and implantation in mammals via posttranscriptional gene regulation mechanisms. Applying custom made multispecies arrays we aimed to analyze expression profile of microRNAs in peri-implantation porcine conceptuses/trophoblasts to identify their potential role at the maternal-fetal interface during the critical period of maternal recognition of pregnancy and implantation.
2014-12-05 | GSE59618 | GEO
Project description:Physical training improves insulin sensitivity and can prevent type 2 diabetes. However, approximately 20% of individuals lack a beneficial outcome in glycemic control. TGF-β, identified as a possible upstream regulator involved in this low response is also a potent regulator of microRNAs (miRs). Aim of this study was to elucidate the potential impact of TGF-β-driven miRNAs on individual exercise response. Non-targeted long and sncRNA sequencing analyses of TGF-β1-treated human skeletal muscle cells corroborated the effects of TGF-β1 on muscle cell differentiation and the induction of extracellular matrix components, and identified several TGF-β1-regulated miRs. qPCR validated a potent upregulation of miR143/145 and miR181a2 by TGF-β1 in both human myoblasts and differentiating myotubes. Human skeletal muscle biopsy donors participating in a supervised 8-week endurance training intervention (n=40) were categorized as responder based on fold change ISIMats (≥ +1.1) or low responder. In skeletal muscle of low responders, TGF-β signaling and miR143/145 levels were stronger induced by training than in responders. Target-mining revealed HDACs, MYHs and insulin signaling components INSR and IRS1 as potential miR143/145 targets. All these targets were down-regulated in TGF-β1-treated myotubes. Transfection of miR mimics in differentiated myotubes validated MYH1, MYH4, and IRS1 as miR143/145 targets. Elevated TGF-β signaling and miR143/145 induction in skeletal muscle of low responders might obstruct improvements in insulin sensitivity by training in two ways: By negatively impacting cell fusion and myofiber functionality via miR143 suppressing its novel targets MYH1/4; by directly impairing insulin signaling via reduction of INSR by TGF-β and fine-tuned IRS1 suppression by miR143.
2021-12-07 | GSE188235 | GEO
Project description:Physical training improves insulin sensitivity and can prevent type 2 diabetes. However, approximately 20% of individuals lack a beneficial outcome in glycemic control. TGF-β, identified as a possible upstream regulator involved in this low response is also a potent regulator of microRNAs (miRs). Aim of this study was to elucidate the potential impact of TGF-β-driven miRNAs on individual exercise response. Non-targeted long and sncRNA sequencing analyses of TGF-β1-treated human skeletal muscle cells corroborated the effects of TGF-β1 on muscle cell differentiation and the induction of extracellular matrix components, and identified several TGF-β1-regulated miRs. qPCR validated a potent upregulation of miR143/145 and miR181a2 by TGF-β1 in both human myoblasts and differentiating myotubes. Human skeletal muscle biopsy donors participating in a supervised 8-week endurance training intervention (n=40) were categorized as responder based on fold change ISIMats (≥ +1.1) or low responder. In skeletal muscle of low responders, TGF-β signaling and miR143/145 levels were stronger induced by training than in responders. Target-mining revealed HDACs, MYHs and insulin signaling components INSR and IRS1 as potential miR143/145 targets. All these targets were down-regulated in TGF-β1-treated myotubes. Transfection of miR mimics in differentiated myotubes validated MYH1, MYH4, and IRS1 as miR143/145 targets. Elevated TGF-β signaling and miR143/145 induction in skeletal muscle of low responders might obstruct improvements in insulin sensitivity by training in two ways: By negatively impacting cell fusion and myofiber functionality via miR143 suppressing its novel targets MYH1/4; by directly impairing insulin signaling via reduction of INSR by TGF-β and fine-tuned IRS1 suppression by miR143.
2021-12-07 | GSE188234 | GEO
Project description:We investigated Smad4-mediated TGF-beta signaling in the development of occipital somite-derived myogenic progenitors during tongue morphogenesis by comparing the transcriptomes of tongue derived from Myf5-Cre;Smad4flox/flox mutant and Myf5-Cre;Smad4flox/+ control mice at day E13.5. Based on gene expression profiles and functional studies, we elucidated the influences Smad4 activity and TGF-beta signaling have on the gene expression profiles underlying tongue development. The data are consistent with the hypothesis that TGF-beta-Smad4-FGF6 signaling cascade plays a crucial role in myogenic cell fate determination and lineage progression during tongue myogenesis. We obtained RNA samples from tongue tissues of mutant and control mouse embryos (C57BL/6J) at day E13.5 RNA and subjected them to analysis on Affymetrix GeneChip Mouse Genome 430 2.0 Arrays.
2012-02-03 | E-GEOD-35357 | biostudies-arrayexpress
Project description:Polycomb-group proteins are key regulators of the transcriptional programs that maintain stem cell identity and dictate lineage specification. Polycomb repressor complex 1 (PRC1) contains the E3 ligases RING1A/B, which monoubiquitinate lysine 119 at histone H2A (H2AK119ub1) to regulate gene expression. PRC1 has been sub-classified into six major complexes based on the presence of a PCGF subunit. Here, we find that Pcgf5, one of six PCGF paralogs, is an important requirement in the differentiation of mouse embryonic stem cells (mESCs) towards a neural cell fate. Although PCGF5 is not required for mESC self-renewal, its loss blocks mESC neural differentiation by activating the SMAD2/TGF-β signaling pathway. Inhibition of SMAD2/TGF-β signaling or rescue by overexpression of Pcgf5 can restore the capability of mESCs to differentiate towards a neural cell fate. PCGF5 works by stimulating RING1B-dependent H2AK119ub1 both in vitro and in vivo, leading to the suppression of TGF-β signaling genes. PCGF5 loss-of-function prevents the reduction of H2AK119ub1 and H3K27me3 around neural specific genes and keeps them repressed. Our results showed that PCGF5 might function as both a repressor for SMAD2/TGF-β signaling pathway and a facilitator for neural differentiation. Together, our findings reveal a critical context-specific function for PCGF5 in directing PRC1 to control cell fate.
2018-03-10 | GSE95127 | GEO