Mouse Embryonic Stem Cells Resist c-Jun induced Differentiation in Suspension
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA471246 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7160934.fastq.gz | Fastqsanger.gz | |||
| SRR7160935.fastq.gz | Fastqsanger.gz |
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Project description:The oncogene c-Jun plays a key role in development and cancer. Yet, its role in cell fate decision remains poorly understood at the molecular level. Here we report that c-Jun confers different fate decisions upon mouse embryonic stem cells (mESCs) in adhesion vs suspension. We developed a Tet-on system for temporal induction of c-Jun expression by Doxycycline treatment in mESCs. We show that mESCs carrying the inducible c-Jun TetOn remain pluripotent and grow slowly in suspension with induction of c-Jun, while undergoing differentiation with normal proliferative potentials in adherence upon c-Jun induction. Apparently, c-Jun pushes mESCs in suspension into cell cycle arrest at G1/S, through the induction of Cdkn1a/b and Cdkn2/a/b/c. Despite cell cycle arrest, they can re-enter cell cycle upon plating on adhesive surface and grow into typical mESC colonies albeit at lower efficiency. These results demonstrate that mESCs respond to c-Jun differently in suspension or adherence. Our results suggest that cells in suspension may be more resistant to differentiation than in adherence.
2019-02-19 | GSE114381 | GEO
Project description:The oncogene c-Jun plays a key role in development and cancer. Yet, its role in cell fate decision remains poorly understood at the molecular level. Here we report that c-Jun confers different fate decisions upon mouse embryonic stem cells (mESCs) in adhesion vs suspension culture. We developed a Tet-on system for temporal induction of c-Jun expression by Doxycycline treatment in mESCs. We show that mESCs carrying the inducible c-Jun TetOn remain pluripotent and grow slowly in suspension when c-Jun expression is induced, whilst when the cells adhere they undergo differentiation and show normal proliferative potential upon c-Jun induction. Our data indicates that c-Jun pushes mESCs in suspension into cell cycle arrest at G1/S, by activating the cell cycle inhibitors Cdkn1a/b and Cdkn2/a/b/c. Despite this cell cycle arrest, they can still re-enter the cell cycle upon transfer to an adhesive surface, and grow into typical mESC colonies, albeit at a lower efficiency. These results demonstrate that mESCs respond to induced c-Jun overexpression differently in suspension or adherent cultures. Our results suggest that cells in suspension may be more resistant to differentiation than when they adhere.
| S-EPMC6326245 | biostudies-literature
Project description:Serine/threonine kinase 40 (Stk40) was previously identified as a direct target gene of pluripotency-associated transcription factor Oct4 and its overexpression could facilitate differentiation of mouse embryonic stem cells (mESCs) towards the extraembryonic endoderm. Stk40-/- mice are lethal at the perinatal stage, displaying multiple organ failures. However, the molecular mechanisms underlying the physiological functions of Stk40 remain elusive. Here, we report that Stk40 ablation compromises the mesoderm differentiation from mESCs in vitro and in embryos. Mechanistically, Stk40 interacts with both mammalian constitutive photomorphogenic protein 1 (Cop1) and c-Jun, promoting degradation of c-Jun. Consequently, Stk40 knockout leads to c-Jun protein accumulation, which, in turn, might suppress the Wnt signaling activity and impair the mesoderm differentiation process. Overall, this study reveals that Stk40, together with Cop1, represent a novel axis for modulating c-Jun protein levels within an appropriate range during mesoderm differentiation from mESCs. Our finding provides new insight into the molecular mechanism regulating c-Jun protein stability and may have potential for managing related cellular disorders.
2019-05-14 | PXD012579 | Pride
Project description:Mesoderm development is a finely tuned process initiated by the differentiation of pluripotent epiblast cells. Serine/threonine kinase 40 (STK40) controls the development of several mesoderm-derived cell types, its overexpression induces differentiation of mouse embryonic stem cells (mESCs) towards the extraembryonic endoderm, and Stk40 knockout (KO) results in multiple organ failure and is lethal at the perinatal stage in mice. However, molecular mechanisms underlying the physiological functions of STK40 in the mesoderm differentiation remain elusive. Here, we report that Stk40 ablation impairs mesoderm differentiation both in vitro and in vivo. Mechanistically, STK40 interacts with both the E3 ubiquitin ligase mammalian constitutive photomorphogenesis protein 1 (COP1) and the transcriptional regulator proto-oncogene c-Jun (c-JUN), promoting c-JUN protein degradation. Consequently, Stk40 knockout leads to c-JUN protein accumulation, which, in turn, apparently suppresses the WNT signaling activity and impairs the mesoderm differentiation process. Overall, this study reveals that STK40, together with COP1, represents a previously unknown regulatory axis that modulates the c-JUN protein level within an appropriate range during mesoderm differentiation from mESCs. Our findings provide critical insights into the molecular mechanisms regulating the c-JUN protein level and may have potential implications for managing cellular disorders arising from c-JUN dysfunction.
2019-05-10 | GSE125877 | GEO
Project description:Embryonic stem cells (ESC) are able to give rise to any somatic cell type. A lot is known about how ESC pluripotency is maintained, but comparatively less is known about how differentiation is promoted. Cell fate decisions are regulated by interactions between signalling and transcriptional networks. Recent studies have shown that the overexpression or downregulation of the transcription factor Jun can affect the ESC fate. Here we have focussed on the role of the Jun in the exit of mouse ESCs from ground state pluripotency and the onset of early differentiation. Transcriptomic analysis of differentiating ESCs reveals that Jun is required to upregulate a programme of genes associated with cell adhesion as ESCs exit the pluripotent ground state.
2015-12-07 | E-MTAB-4068 | biostudies-arrayexpress
Project description:During in vitro differentiation, pluripotent stem cells undergo extensive remodeling of their gene expression profiles. While studied extensively at the transcriptome level, much less is known about protein dynamics, which might differ significantly from their mRNA counterparts. Here, we present deep proteome-wide measurements of protein levels during the differentiation of embryonic stem cells.
2017-01-10 | MSV000080461 | MassIVE
Project description:Human embryonic and induced pluripotent stem cells (hESCs/hiPSCs) hold great promise for cell-based therapies and drug discovery. However, homogeneous differentiation remains a major challenge, highlighting the need for understanding developmental mechanisms. We performed genome-scale CRISPR screens to uncover regulators of definitive endoderm (DE) differentiation, which unexpectedly uncovered five JNK/JUN family genes as key barriers of DE differentiation. The JNK/JUN pathway does not act through directly inhibiting the DE enhancers. Instead JUN co-occupies ESC enhancers with OCT4, NANOG and SMAD2/3, and specifically inhibits the exit from the pluripotent state by impeding the decommissioning of ESC enhancers and inhibiting the reconfiguration of SMAD2/3 chromatin binding from ESC to DE enhancers. Therefore, the JNK/JUN pathway safeguards pluripotency from precocious DE differentiation. Direct pharmacological inhibition of JNK significantly improves the efficiencies of generating DE and DE-derived pancreatic and lung progenitor cells, highlighting the potential of harnessing the knowledge from developmental studies for regenerative medicine.
2019-03-18 | GSE109524 | GEO
Project description:c-Jun is a gene expression regulator. By forming homo- or heterodimer, c-Jun binds to DNA and regulates gene transcription. c-Jun is deeply involved in embryonic development but its effect on nervous system development especially in higher mammal is unclear. In this study, we combined H1ESC derived neural progenitor cells (NPCs), cerebral organoids (COs) and mouse model to study the role of c-Jun in early nervous system development. c-Jun KO promoted NPCs induction and differentiation while weakened NPCs’ adhesion ability. c-Jun KO COs got more robust neural ectoderm and expanded Pax6+/Nestin+ cortex-like layer while less tight junctional core. c-Jun KO mouse embryos on E14.5 showed malformation of thalamus in diencephalon with tight junction loose and cell lose. Taken together, the consistent trend in three models implied that c-Jun deletion promoted neural differentiation while weakened the tight junctions. The thalamus/diencephalon was vulnerable to dysplasia when lose c-Jun in early mouse embryonic development.
2024-12-20 | GSE243735 | GEO
Project description:In the first group of samples, we are looking into the different metabolites and their concentrations within our human embryonic stem cells over the course of differentiation. Our goal is to study how the metabolism of stem cells are changing as they undergo this conversion to become hepatocyte-like cells. In the second group of samples labeled HyCell, we would like to understand the concentrations of metabolites within our CHO cells in order to update the parameters for our metabolic model. Included are two samples from different days of a suspension batch culture which may have different lactate production qualities.
2017-08-02 | ST000837 | MetabolomicsWorkbench
Project description:The purpose of this microarray study was to analyze the initial changes in gene expression that occurred during the first 48 hours of a pancreatic progenitor differentiation scheme. The experiment compared both progenitors cultured normally in 10% SCM with nicotinamide as well as progenitors cultured in suspension for 48 hours in 10% SCM with nicotinamide. For the described conditions, 4 sample pairs were analyzed by microarray, for a total of 8 hybridizations. Each biological set was comprised of one normal and one suspension culture sample. Each set was hybridized only once.
2014-07-15 | E-MTAB-2746 | biostudies-arrayexpress