Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Prediction and Testing of Novel Networks Regulating Embryonic Stem Cell Self-Renewal and Commitment

ABSTRACT: Stem cell fate is governed by the integration of intrinsic and extrinsic positive and negative signals upon inherent transcriptional networks. To identify novel embryonic stem cell (ESC) regulators and assemble transcriptional networks controlling ESC fate, we performed temporal expression microarray analyses of ESCs following the initiation of commitment and integrated these data with known genome-wide transcription factor binding. Effects of forced under- or over-expression of predicted novel regulators, defined as differentially expressed genes with potential binding sites for known regulators of pluripotency, demonstrated greater than 90% correspondence with predicted function, as assessed by functional and high content assays of self-renewal. We next assembled 43 theoretical transcriptional networks in ESCs, 82% (23 out of 28 tested) of which were supported by analysis of genome-wide expression in Oct4 knockdown cells. By using this integrative approach we have, for the first time, formulated novel networks describing gene repression of key developmental regulators in undifferentiated ESCs and successfully predicted the outcomes of genetic manipulation of these networks. Keywords: time course

ORGANISM(S): Mus musculus

PROVIDER: GSE7506 | GEO | 2007/04/13

SECONDARY ACCESSION(S): PRJNA100471

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcription profiling of mouse embryonic stem cells after 1, 3, and 5 days LIF differentiation, and 1 and 2 days RA differentiation to predict and test of novel networks regulating embryonic stem cell self-renewal and commitment

Project description:Stem cell fate is governed by the integration of intrinsic and extrinsic positive and negative signals upon inherent transcriptional networks. To identify novel embryonic stem cell (ESC) regulators and assemble transcriptional networks controlling ESC fate, we performed temporal expression microarray analyses of ESCs following the initiation of commitment and integrated these data with known genome-wide transcription factor binding. Effects of forced under- or over-expression of predicted novel regulators, defined as differentially expressed genes with potential binding sites for known regulators of pluripotency, demonstrated greater than 90% correspondence with predicted function, as assessed by functional and high content assays of self-renewal. We next assembled 43 theoretical transcriptional networks in ESCs, 82% (23 out of 28 tested) of which were supported by analysis of genome-wide expression in Oct4 knockdown cells. By using this integrative approach we have, for the first time, formulated novel networks describing gene repression of key developmental regulators in undifferentiated ESCs and successfully predicted the outcomes of genetic manipulation of these networks. Experiment Overall Design: 1, 3, and 5 days LIF differentiated ESCs, and 1 and 2 days RA differentiated ESCs

2008-06-15 | E-GEOD-7506 | biostudies-arrayexpress

Polycomb-like 2 associates with PRC2 and is required for mouse embryonic stem cell

Project description:Polycomb group (PcG) proteins are highly conserved epigenetic transcriptional repressors important for the control of numerous developmental gene expression programs and have recently been implicated in the modulation of embryonic stem cell (ESC) identity. We identified the PcG protein PCL2 (polycomb-like 2) in a genome-wide screen for novel regulators of self-renewal and pluripotency and predicted that it would play an important role in mouse ESC fate determination. Using multiple biochemical strategies, we provide evidence that PCL2 is a novel Polycomb Repressive Complex 2 (PRC2)-associated protein in mouse ESCs. Knockdown of Pcl2 in ESCs resulted in heightened self-renewal characteristics, defects in differentiation and altered patterns of histone methylation. Through integration of global gene expression and promoter occupancy analyses of both PCL2 and PRC2 components EZH2 and SUZ12, we have predicted PCL2 target genes and formulated regulatory networks describing the role of PCL2 both in modulating transcription of ESC self-renewal genes in undifferentiated ESCs as well as developmental regulators during early commitment and differentiation. Cells were stably expressing Pcl2 shRNA or shRNA mismatch control sequences. Hybridizations of three biological replicates for both the control and Pcl2 shRNA clone were performed.

2010-02-22 | E-GEOD-16364 | biostudies-arrayexpress

Polycomb-like 2 associates with PRC2 and is required for mouse embryonic stem cell

2010-02-05 | GSE16364 | GEO

Jun-mediated changes in cell adhesion contribute to embryonic stem cell exit from ground state pluripotency

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

Prediction and Testing of Novel Transcriptional Networks Regulating Embryonic Stem Cell Self-Renewal and Commitment

Project description:We have used mouse embryonic stem cells (ESCs) as a model to study the signaling mechanisms that regulate self-renewal and commitment to differentiation. We hypothesized that genes critical to stem cell fate would be dynamically regulated at the initiation of commitment. Time course microarray analysis following initiation of commitment led us to propose a model of ESC maintenance in which highly regulated transcription factors and chromatin remodeling genes (down-regulated in our time course) maintain repression of genes responsible for cell differentiation, morphogenesis and development (up-regulated in our time course). Microarrays of Oct4, Nanog and Sox2 shRNA knockdown cell lines confirmed predicted regulation of target genes. shRNA knockdowns of candidate genes were tested in a novel high throughput screen of self-renewal, confirming their role in ESC pluripotency. We have identified genes that are critical for self-renewal and those that initiate commitment and developed draft transcriptional networks that control self-renewal and early development. Keywords: genetic modification Gene expression in Oct4 knockdown, Sox2 knockdown and their empty vector contol ES cells was analyzed.

2010-06-11 | E-GEOD-7520 | biostudies-arrayexpress

AMPK governs lineage specification through Tfeb-dependent regulation of lysosomes

Project description:Faithful execution of developmental programs relies on the acquisition of unique cell identities from pluripotent progenitors, a process governed by combinatorial inputs from numerous signaling cascades that ultimately dictate lineage-specific transcriptional outputs. Despite growing evidence that metabolism is integrated with many molecular networks, how pathways that control energy homeostasis may affect cell fate decisions is largely unknown. Here, we show that AMPK, a central metabolic regulator, plays critical roles in lineage specification. Although AMPK-deficient embryonic stem cells (ESCs) were normal in the pluripotent state, these cells displayed profound defects upon differentiation, failing to generate chimeric embryos and preferentially adopting an ectodermal fate at the expense of the endoderm during embryoid body (EB) formation. AMPK-/- EBs exhibited reduced levels of Tfeb, a master transcriptional regulator of lysosomes, leading to diminished endolysosomal function. Remarkably, genetic loss of Tfeb also yielded endodermal defects, while AMPK-null ESCs over-expressing this transcription factor normalized their differential potential, revealing an intimate connection between Tfeb/lysosomes and germ layer specification. The compromised endolysosomal system resulting from AMPK or Tfeb inactivation blunted Wnt signaling, while up-regulating this pathway restored expression of endodermal markers. Collectively, these results uncover the AMPK pathway as a novel regulator of cell fate determination during differentiation. 2 WT and 2 AMPK DKO ESC lines were differentiated into embryoid bodies (EBs) for various lengths of time (2, 4, 8, and 12 days) in high and low glucose conditions. Both ESC and EB samples were profiled by mRNA-seq to examine how global gene expression changes associated with ESC differentiation are affected by AMPK deletion.

2016-03-09 | E-GEOD-77705 | biostudies-arrayexpress

Mouse ESC Nr1h2 interactome under T09 treatment

Project description:The intrinsic regulators of stem cell-based embryo models are not well studied. We show that Nr1h2 activation enables conventional ESCs to form blastoids with better implantation and higher blastocyst rates. We identified Nr1h2 transcriptional interactome by CoIP-MS using FLAG antibody to immunoprecipitate Nr1h2-FLAG and its partners in ESC overexpressing Nr1h2-FLAG.

2024-10-28 | PXD057257 | Pride

MS-based quantitative proteomic analysis of embryonic stem cells with normal and reduced expression of Rsl24d1.

Project description:Embryonic stem cell (ESC) fate decisions are regulated by a complex molecular circuitry that requires tight and coordinated gene expression regulations at multiple levels from chromatin organization to mRNA processing. Recently, ribosome biogenesis and translation have emerged as key pathways that efficiently control stem cell homeostasis. However, the molecular mechanisms underlying the regulation of these pathways remain largely unknown to date. Here, we analyzed the expression, in mouse ESCs, of over 300 genes involved in ribosome biogenesis and we identified RSL24D1 as the most differentially expressed between self-renewing and differentiated ESCs. RSL24D1 is highly expressed in multiple mouse pluripotent stem cell models and its expression profile is conserved in human ESCs. RSL24D1 is associated with nuclear pre-ribosomes and is required for the maturation and the synthesis of 60S subunits in mouse ESCs. Interestingly, RSL24D1 depletion significantly impairs global translation, particularly of key pluripotency factors, including POU5F1 and NANOG, as well as components of the polycomb repressive complex 2 (PRC2). Consistently, RSL24D1 is required for mouse ESC self-renewal and proliferation. Taken together, we show that RSL24D1-dependant ribosome biogenesis is required to both sustain the expression of pluripotent transcriptional programs and silence developmental programs, which concertedly dictate ESC homeostasis.

2023-01-10 | PXD030497 | Pride

Prediction and Testing of Novel Transcriptional Networks Regulating Embryonic Stem Cell Self-Renewal and Commitment

2007-04-18 | GSE7520 | GEO

Gene expression profiles of mouse embryonic stem cells (mESCs) after genetic depletion of Id1 and knock-down of Zrf1

Project description:Id proteins are dominant negative regulators within the HLH family of proteins. In embryonic stem cells (ESCs), Id1 and Id3 maintain the pluripotent state by preventing neural differentiation. The Id1-interacting protein Zrf1 plays a crucial role as a chromatin-bound factor in specification of the neural fate from ESCs. Here, we show that Id1 blocks Zrf1 recruitment to chromatin, thus preventing the activation of neural genes during ESC differentiation. Moreover, genetic deletion of Id1 in ESCs caused misexpression of more than 6000 genes. Interestingly, the expression of almost half of those genes was restored upon further depletion of Zrf1. We therefore identified Zrf1 as a transcriptional regulator downstream of Id1 in ESCs. In Id1KO mESCs, Zrf1 expression was depleted by using shRNAs. Four replicates corresponding to four independent biological samples per group were collected.

2014-11-05 | E-GEOD-58627 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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