Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

14 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Simulated microgravity regulates the self-renewal and pluripotency of mouse and human embryonic stem cells - RNA-seq

ABSTRACT: Human exploration of outer space will inevitably require human reproduction and development in the space environment. Embryonic stem cells (ESCs) are widely employed to study mammalian development and reproduction for their characteristics of indefinite self-renewal and pluripotency. Due to the lack of experimental opportunities and related techniques, studies of the effects of microgravity on the self-renewal and differentiation of ESCs are mostly descriptive, with in-depth mechanistic studies remaining scarce. Here we show in both mouse and human ESCs that simulated microgravity (SMG)-induced stress regulates the self-renewal and pluripotency in a conserved mechanism. Specifically, SMG upregulates the expression of heat shock protein (HSP) and/or HSF1 genes, thereby increasing the expression of core pluripotency factors and the activity of the Wnt pathway. In mESCs, the upregulation of Hsps and Hsf1 genes by SMG increased the activity of the LIF/STAT3 pathway. The upregulation of Tbx3 by increased activity of the Wnt and LIF/STAT3 pathways promotes the differentiation of both mouse and human ESCs to mesendoderm under the SMG environment. Finally, the ATAC-seq and ChIP-seq analysis in this study reveal a minor effect of SMG on the global chromatin accessibility and the overall patterns of the tested histone modifications in mESCs.

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Mus musculus

SUBMITTER: Xi Chen

PROVIDER: E-MTAB-12389 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Simulated microgravity regulates the self-renewal and pluripotency of mouse and human embryonic stem cells - ChIP-seq

Project description:Human exploration of outer space will inevitably require human reproduction and development in the space environment. Embryonic stem cells (ESCs) are widely employed to study mammalian development and reproduction for their characteristics of indefinite self-renewal and pluripotency. Due to the lack of experimental opportunities and related techniques, studies of the effects of microgravity on the self-renewal and differentiation of ESCs are mostly descriptive, with in-depth mechanistic studies remaining scarce. Here we show in both mouse and human ESCs that simulated microgravity (SMG)-induced stress regulates the self-renewal and pluripotency in a conserved mechanism. Specifically, SMG upregulates the expression of heat shock protein (HSP) and/or HSF1 genes, thereby increasing the expression of core pluripotency factors and the activity of the Wnt pathway. In mESCs, the upregulation of Hsps and Hsf1 genes by SMG increased the activity of the LIF/STAT3 pathway. The upregulation of Tbx3 by increased activity of the Wnt and LIF/STAT3 pathways promotes the differentiation of both mouse and human ESCs to mesendoderm under the SMG environment. Finally, the ATAC-seq and ChIP-seq analysis in this study reveal a minor effect of SMG on the global chromatin accessibility and the overall patterns of the tested histone modifications in mESCs.

2023-10-19 | E-MTAB-12390 | biostudies-arrayexpress

Oncostatin M maintains naïve pluripotency of mESCs by tetraploid embryo complementation (TEC) assay

Project description:It has been well established that (LIF) is essential for maintaining naive pluripotency of ESCs. Oncostatin M (OSM) is a member of the IL-6 family of cytokines which share gp130 as a receptor subunit, and the OSM-gp130 complex can recruit either LIF receptor β or OSM receptor β. Here we show that OSM can completely replace LIF to maintain naive pluripotency of mouse ESCs. Mouse ESCs cultured in the presence of LIF or OSM not only express pluripotency genes at similar levels but also exhibit the same developmental pluripotency as evidenced by generation of germline competent chimeras, supporting previous findings. Moreover, we demonstrate that mESCs cultured in OSM produce viable all-ESC pups by tetraploid embryo complementation (TEC) assay, the most stringent functional test of authentic pluripotency. Furthermore, the telomere length and telomerase activity also are crucial for unlimited self-renewal and genomic stability of mESCs, and these do not differ in mESCs cultured under OSM or LIF. The transcriptome of mESCs cultured in OSM overall is very similar to that of LIF, and OSM activates Stat3 signaling pathway, like LIF. Additionally, OSM upregulates pentose and glucuronate interconversions, ascorbate and aldarate metabolism, steroid and retinol metabolism pathways. Although the significance of these pathways remains to be determined, our data shows that OSM can maintain the naive pluripotent stem cells in the absence of LIF.

2021-01-23 | GSE165292 | GEO

ChIP Seq of Oct4, Nanog, H3K27me3 in Oct4+/+ and Oct4 +/- mES cells

Project description:Embryonic stem cell (ESC) pluripotency is governed by a gene regulatory network centred on the transcription factors Oct4 and Nanog. ESCs fluctuate between states of high and low Nanog expression that direct efficient or inefficient self-renewal. To date, robust self-renewing ESC states have only been attained by chemical inhibition of signalling pathways or enforced transgene expression. Here we show that ESCs expressing a reduced range of Oct4 concentrations, typified by Oct4 heterozygous ESCs exhibit stable robust pluripotency. Despite this reduced Oct4 concentration range, this state is characterised by increased genome-wide binding of Oct4, particularly at pluripotency-associated enhancers, homogeneous expression of pluripotency transcription factors, enhanced self-renewal efficiency and delayed differentiation kinetics. In this state, ESCs exhibit increased wnt expression, enhanced LIF-sensitivity, non-responsiveness to FGF signalling and can clonally maintain pluripotency without BMP but remain dependent upon LIF. Robust pluripotency is destabilised either by alteration of the Oct4 level or by removal of LIF. Our findings suggest that robust pluripotency originates from cells with a reduced Oct4 protein concentration and that the wild-type Oct4 range enables effective differentiation.

2013-05-07 | E-MTAB-1617 | biostudies-arrayexpress

RNA-seq experiment of mouse embryonic stem cells (mESCs), comparing TCF/LEF quadruple knock-out cells with wild type cells

Project description:Mouse embryonic stem cells (mESCs), derived from pre-implantation blastocyst cells, can be maintained in vitro in defined N2B27 medium supplemented with two chemical inhibitors for GSK3 and MEK (2i) and the cytokine leukemia inhibitory factor (LIF), which act synergistically to promote self-renewal and pluripotency. Many efforts have been devoted to identify genes that promote exit from the pluripotent state and the transition to a primed state of differentiation. One of the first identified players in this process was the Wnt/b-catenin effector TCF7L1 (previously referred to as TCF3), belonging to the family of four TCF/LEF transcription factors, which acts as pro-differentiation factor by repressing pluripotency genes. Of note, there is little evidence that the genetic abrogation of the mechanisms required for the exit from the pluripotent state is sufficient to enable self-renewal in the absence of 2iL. Here, we found that complete loss-of-function of Tcf7, Lef1, Tcf7l1 and Tcf7l2, the genes encoding for the four TCF/LEF transcription factors, (refered to as qKO) allows mESCs to become fully 2iL-independent and to propagate in basal N2B27. To understand the genetic program that allows qKO cells to achieve 2iL-independent self-renewal, we performed RNA sequencing (RNA-seq) of qKO and wild type mESCs.

2021-06-15 | E-MTAB-10564 | biostudies-arrayexpress

Mpp8 regulates the activity of LIF/STAT3 pathway in mouse embryonic stem cells

Project description:Mouse embryonic stem cells (mESCs) possess remarkable characteristics of unlimited self-renewal and pluripotency, which render them highly valuable for both fundamental research and clinical applications. A comprehensive understanding of the molecular mechanisms underlying mESC function is of utmost importance. The Human Silence Hub (HUSH) complex, comprising FAM208A, MPP8, and periphilin, constitutes an epigenetic silencing complex involved in suppressing retroviruses and transposons during early embryonic development. However, its precise role in regulating mESC pluripotency and differentiation remains elusive. In this study, we generated homogenous miniIAA7 tagged Mpp8 mouse ES cell lines. Upon induction of MPP8 protein degradation, we observed impaired proliferation and reduced colony formation ability of mESCs. Furthermore, this study unveils the involvement of MPP8 in regulating the activity of the LIF/STAT3 signaling pathway and Nanog expression in mESCs. Finally, we provide compelling evidence that degradation of the MPP8 protein impairs the differentiation of mESC.

2023-12-31 | E-MTAB-13214 | biostudies-arrayexpress

DNMTs Play an Important Role in Maintaining the Pluripotency of Leukemia Inhibitory Factor Dependent Embryonic Stem Cells

Project description:Naïve pluripotency can be maintained in 2i/LIF supplements, which primarily affect canonical WNT, FGF/ERK, and JAK/STAT3 signaling. However, whether one of these tripartite supplements alone is sufficient to maintain naïve self-renewal remain unclear. Here we show that LIF alone medium is sufficient for adaptation of 2i/L-ESCs to ESCs with hypermethylated state (L-ESCs). Global transcriptomic analysis show that L-ESCs are close to 2i/L-ESCs and in a stable state between naïve and primed pluripotency. Notably, our results demonstrate that DNA methyltransferases (DNMTs) play an important role for LIF-dependent mouse ESCs adaptation and self-renew. LIF-dependent ESCs adaptation efficiency is significantly increased in serum treatment and reduced in Dnmt3a or Dnmt3l knockout ESCs. Importantly, unlike epiblast stem cells, L-ESCs contribute to somatic tissues and germ cells in chimaeras. L-ESCs cultured in such a simple conditions in this study would provide a more conducive platform to clarify the molecular mechanism of ESCs in vitro culture.

2021-01-25 | GSE142799 | GEO

Glycolysis-stimulated Esrrb Lactylation Promotes the Self-renewal and XEN Differentiation of Embryonic Stem Cells

Project description:Embryonic stem cells (ESCs) favor glycolysis over oxidative phosphorylation for energy production, and glycolytic metabolism is critical for pluripotency establishment, maintenance and exit. However, how glycolysis regulates the self-renewal and differentiation of ESCs remains elusive. Here, we demonstrated that protein lactylation, regulated by intracellular lactate, contributes to the self-renewal of ESCs. Next, the lactylome profiles of ESCs with and without a lactate dehydrogenase (Ldh) inhibitor, which suppresses the conversion of pyruvate to lactate, were depicted. It was notable that many lactylated proteins are involved in the self-renewal and differentiation of ESCs. We further showed that Esrrb, an orphan nuclear receptor involved in pluripotency maintenance and extraembryonic endoderm stem cell (XEN) differentiation, is lactylated on K228 and K232. Lactylation of Esrrb enhances its activity in promoting ESC self-renewal in the absence of LIF and XEN differentiation of ESCs, through increasing its binding at target genes. Our studies reveal the importance of protein lactation in the self-renewal and XEN differentiation of ESCs, and the underlying mechanism for glycolytic metabolism regulating cell fate choice.

2024-03-01 | GSE237618 | GEO

A balanced Oct4 protein interaction network is crucial for maintaining pluripotency

Project description:Oct4 is considered a master transcription factor for pluripotent cell self-renewal and embryo development. It primarily collaborates with other transcriptional factors or coregulators to maintain pluripotency. However, it is still unclear how Oct4 interacts with its partners. Here, we show that the Oct4 linker interface mediates competing and balanced Oct4 protein interactions which are crucial for maintaining pluripotency. Linker mutant ESCs maintain the key pluripotency genes expression, but show decreased expression of self-renewal genes and increased expression of differentiation genes which result in impaired ESCs self-renewal and early embryonic lethality. Linker mutation dose not affect Oct4 genomic binding and transactivation potential, but breaks the balanced Oct4 interactome. In mutant ESCs, the interaction between Oct4 and Klf5 was decreased, but interactions between Oct4 and Cbx1, Ctr9, Cdc73 were increased which disrupt the epigenetic state of ESCs. Overexpression of Klf5 or knockdown Cbx1, Cdc73 rescue the cellular phenotype of linker mutant ESCs by rebalancing Oct4 interactome indicating that different partners interact with Oct4 competitively. Thus, by showing how Oct4 interacts with different partners, we provide novel molecular insights to explain how Oct4 contributes to the maintenance of pluripotency.

2021-12-10 | PXD017456 | Pride

Genome-wide analysis of gene expression regulated by calcineurin-NFAT signaling in mouse embryonic stem cells

Project description:Self-renewal and pluripotency are hallmarks of embryonic stem cells (ESCs). However, signaling pathways triggering their transition from self-renewal to differentiation are not well defined. Here, we report that the calcineurin-NFAT signaling pathway is both necessary and sufficient to switch ESCs from an undifferentiated state to early differentiation.To gain an insight into the function of calcinerin-NFAT signaling in ESC lineage commitment, we examined the repertoire of genes changed after LIF withdrawal alone, LIF withdrawal in the presence of cyclosporine A (CsA), a specific inhibitor of calcinerin and forced expression of active forms of calcineurin (deltaCnA) in the presence of LIF,and identified distinct classes of up and down regulated genes by calcineurin-NFAT signaling in mouse embryonic stem cells.

2011-01-01 | GSE21378 | GEO

Genome-wide analysis of gene expression regulated by calcineurin-NFAT signaling in mouse embryonic stem cells

2011-01-01 | E-GEOD-21378 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data