Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Maternal undernutrition induces cell signalling and metabolic dysfunction in undifferentiated mouse embryonic stem cells

ABSTRACT: The peri-conceptional environment can induce permanent changes in embryo phenotype which alter development and associate with later disease susceptibility. Thus, mouse maternal low protein diet (LPD) fed exclusively during preimplantation is sufficient to cause cardiovascular, metabolic and neurological dysfunction in adult offspring. Embryonic stem cell (ESC) lines were generated from LPD and control NPD C57BL/6 blastocysts and characterised by transcriptomics, metabolomics, bioinformatics and molecular/cellular studies to assess early potential mechanisms in dietary environmental programming. Previously, we showed these lines retain cellular and epigenetic characteristics of LPD and NPD embryos after several passages. Here, three main changes were identified in LPD ESC lines. First, their derivation capacity was reduced but pluripotency marker expression was similar to controls. Second, LPD lines had impaired Mitogen-activated protein kinase (MAPK) pathway with altered gene expression of several regulators (e.g., Maff, Rassf1, JunD), reduced ERK1/2 signalling capacity and poorer cell survival characteristics which may contribute to reduced derivation. Third, LPD lines had impaired glucose metabolism comprising reduced upstream enzyme expression (e.g., Gpi, Mpi) and accumulation of metabolites (e.g., glucose-6-P, fructose-6-P) above the phosphofructokinase (PFK) gateway with PFK enzyme activity reduced. ESC lines may therefore permit investigation of peri-conceptional programming mechanisms with reduced need for animal experimentation.

ORGANISM(S): Mus musculus

PROVIDER: GSE216108 | GEO | 2022/12/15

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Scaled and efficient derivation of loss-of-function alleles in risk genes for neurodevelopmental and psychiatric disorders in human iPSCs

Project description:Translating genetic findings for neurodevelopmental and psychiatric disorders (NPD) into actionable disease biology would benefit from large-scale and unbiased functional studies of NPD genes. Leveraging the cytosine base editing (CBE) system, here we developed a pipeline for clonal loss-of-function (LoF) allele mutagenesis in human induced pluripotent stem cells (hiPSCs) by introducing premature stop-codons (iSTOP) that lead to mRNA nonsense-mediated-decay (NMD) or protein truncation. We tested the pipeline for 23 NPD genes on 3 hiPSC lines and achieved highly reproducible, efficient iSTOP editing in 22 NPD genes. Using RNAseq, we confirmed their pluripotency, absence of chromosomal abnormalities, and NMD. Interestingly, for three schizophrenia risk genes (SETD1A, TRIO, CUL1), despite the high efficiency of base editing, we only obtained heterozygous LoF alleles, suggesting their essential roles for cell growth. We replicated the reported neural phenotypes of SHANK3-haploinsufficiency and found CUL1-LoF reduced neurite branches and synaptic puncta density. This iSTOP pipeline enables a scaled and efficient LoF mutagenesis of NPD genes, yielding an invaluable shareable resource.

2024-09-17 | GSE262442 | GEO

DNA methylation dynamics of the human pre-implantation embryo

Project description:We present genome-scale maps of DNA methylation in early human development and perform comparative analysis to mouse that confirm a conserved global erasure of the paternal genome. We find that while many global features of the early embryo are consistent between the two species, the target sequences in which DNA methylation is maintained are distinct. Repetitive elements show a broader range of class specific behaviors in the human embryo and a larger degree of methylation escape in human sperm. We identify thousands of differentially methylated regions (DMRs) that are likely of maternal origin and found that these gamete contributed DMRs are far more species-specific than expected given the conservation of canonical imprint control regions (ICRs). Finally, we extended our studies to the derivation of new human embryonic stem cell (ESC) lines and found notable divergences in DNA methylation signatures from those found in the human embryo and different mouse ESC derivation conditions. Comparison of DNA methylation patterns in human early development, human ESC derivation and mouse ESC derivation

2014-07-23 | E-GEOD-51239 | biostudies-arrayexpress

Transcriptional profiling of rhesus monkey nuclear transfer embryonic stem cells

Project description:Derivation of embryonic stem cells (ESC) genetically identical to a patient by somatic cell nuclear transfer (SCNT) holds the potential to cure or alleviate the symptoms of many degenerative diseases while circumventing any immunorejection issues. However, no primate nuclear transfer embryonic stem (ntES) cell lines have been derived to date. Here, we used a modified SCNT technique to produce rhesus macaque SCNT blastocysts at a relatively high efficiency from adult donor cells and we successfully derived two primate ntES cell lines from 304 oocytes (an overall efficiency of 0.7%). Nuclear and mitochondrial DNA analysis confirmed the ntES cell lines were derived from rhesus monkey SCNT blastocysts and both rhesus monkey ntES cell lines exhibited a normal ESC morphology, expressed key stemness markers, were transcriptionally indistinguishable from control ESC lines and differentiated into multiple cell types. This is, to our knowledge, the first confirmed derivation of primate ntES cell lines. Keywords: rhesus monkey somatic cell nuclear transfer embryonic stem cells

2007-08-29 | GSE7748 | GEO

Copy number variant (CNV) and Single nucleotide polymorphism (SNP) of UCLA hESC lines

Project description:Female human ESC-lines can carry active X-chromosomes (Xa) or an XIST-RNA- coated inactive X-chromosome (Xi XIST+ ). Additionally, many ESC-lines have abnormal X-chromosome-inactivation (XCI)-states where the Xi no longer expresses XIST-RNA and has transcriptionally active regions (eroded Xi=Xe). The fate of each XCI-state upon differentiation is unclear because individual lines often contain a mixture of XCI-states. Here, we established homogeneous XiXa, XeXa, and XaXa ESC-lines. We found that these lines were unable to initiate XIST-expression and X-chromosome- wide silencing upon differentiation indicating that the ESC XCI-state is maintained in differentiated cells. Consequently, differentiated XeXa and XaXa cells displayed higher levels of X-linked gene-expression than XiXa cells. Although global transcriptional compensation between X-chromosomes and autosomes is not required for female ESC-differentiation, the degree of X-chromosome- silencing influences differentiation efficiencies. Our data suggest that the Xi XIST+ Xa state is inherent to human ESCs and that all other XCI-states, including XaXa, are abnormal and arise during ESC-derivation or maintenance.

2016-12-15 | GSE91072 | GEO

Project description:Nodule RNAseq from M. truncatula NPD knockout lines

| PRJNA418151 | ENA

Human embryonic stem cells do not change their X-inactivation status during differentiation [RRBS-Seq]

Project description:Female human ESC-lines can carry active X-chromosomes (Xa) or an XIST-RNA-coated inactive X-chromosome (XiXIST+). Additionally, many ESC lines have abnormal X-chromosomeinactivation (XCI)-states where the Xi no longer expresses XIST-RNA and has transcriptionally active regions (eroded Xi=Xe). The fate of each XCI-state upon differentiation is unclear because individual lines often contain a mixture of XCI-states. Here, we established homogeneous XiXa, XeXa, and XaXa ESC-lines. Employing RNA-FISH, RNA-sequencing and DNA methylation analyses, we found that these lines were unable to initiate XIST-expression and X-chromosome-wide silencing upon differentiation indicating that the ESC XCI-state is maintained in differentiated cells. Consequently, differentiated XeXa and XaXa cells displayed higher levels of X-linked gene-expression than XiXa cells. Although global transcriptional compensation between X-chromosomes and autosomes is not required for female ESC-differentiation, the degree of X-chromosome-silencing influences differentiation efficiencies. Our data suggest that the XiXIST+Xa state is inherent to human ESCs and that all other XCI-states, including XaXa, are abnormal and arise during ESC-derivation or maintenance.

2017-01-26 | GSE88932 | GEO

Human embryonic stem cells do not change their X-inactivation status during differentiation [RNA-Seq]

2017-01-26 | GSE88931 | GEO

Human and marmoset trophoblast stem cells differ in signalling requirements and recapitulate divergent modes of trophoblast invasion

Project description:We derive experimental conditions for the derivation of marmoset trophoblast like cells. Marmoset naïve PSC form extraembryonic mesoderm in human TSC conditions, whilst TGFβ/NODAL, FGF/ERK and WNT signalling control marmoset peri- and postimplantation trophoblast identity.

2024-11-21 | E-MTAB-12463 | biostudies-arrayexpress

DNA methylation dynamics of the human pre-implantation embryo

2014-07-23 | GSE51239 | GEO

Gene expression of PCSM-LPD

Project description:Primary cutaneous CD4+ small or medium T-cell lymphoproliferative disorder (PCSM-LPD) is a clonal T-cell proliferation disease confined to the skin. PCSM-LPD shares expression of T-follicular T helper cell (Tfh) markers with various mature T-cell lymphomas. However, the benign presentation of PCSM-LPD contrasts the clinical behavior of other Tfh-lymphomas. The aim of our study was to delineate the molecular similarities and differences between PCSM-LPD and other Tfh-derived lymphomas, to explain the clinical behavior and to unravel possible pathological mechanisms. We performed targeted next generation sequencing of 19 genes recurrently mutated in T-cell neoplasms in n=17 PCSM-LPD with high and in n=21 PCSM-LPD with low tumor cell content. Furthermore, gene expression profiling was used to identify genes potentially expressed in the PD1+ neoplastic cells. Expression of some of these genes was confirmed in situ using multi-stain immunofluorescence. We found that PCSM-LPD rarely harbors mutations recurrently detected in other T-cell neoplasms. PCSM-LPD is characterized by the invariable expression of the T-cell receptor associated LCK protein. CD70 and its ligand CD27 are co-expressed on PD1+ PCSM-LPD cells, suggestive of auto-activation of the CD70 pathway. In conclusion, PCSM-LPD differs from disseminated lymphomas of Tfh origin by their mutation profile. Activation of CD70 signaling also found in cutaneous T-cell lymphoma represents a potential driver of neoplastic proliferation of this benign neoplasia of Tfh.

2023-11-06 | GSE243819 | GEO

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