Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Molecular Criteria for Defining the Naive Human Pluripotent State

ABSTRACT: Naive human pluripotent cells have been isolated in culture, but it remains unclear to what extent they resemble pluripotent cells in vivo. Here we present three lines of evidence indicating that naive pluripotent stem cells generated by small molecules share defining molecular signatures with the human preimplantation embryo. First, a comprehensive analysis of the transposcriptome reveals that naive human cells display a unique transposon expression profile of cleavage stage embryos. Second, induction of naive pluripotency is accompanied by a genome-wide depletion in DNA methylation that is reversible upon differentiation except at imprinted regions. Third, allele-specific analysis demonstrates that female naive cells exhibit an X chromosome signature of the human preimplantation embryo. However, when introduced into mouse embryos the naive cells failed to efficiently generate interspecies chimeras. Our work provides a set of molecular benchmarks for evaluating the developmental identity of distinct human pluripotent states captured in vitro.

ORGANISM(S): Homo sapiens

PROVIDER: GSE75868 | GEO | 2016/07/18

SECONDARY ACCESSION(S): PRJNA305609

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Molecular Criteria for Defining the Naive Human Pluripotent State [methylation profiling]

Project description:Naive human pluripotent cells have been isolated in culture, but it remains unclear to what extent they resemble pluripotent cells in vivo. Here we present three lines of evidence indicating that naive pluripotent stem cells generated by small molecules share defining molecular signatures with the human preimplantation embryo. First, a comprehensive analysis of the transposcriptome reveals that naive human cells display a unique transposon expression profile of cleavage stage embryos. Second, induction of naive pluripotency is accompanied by a genome-wide depletion in DNA methylation that is reversible upon differentiation except at imprinted regions. Third, allele-specific analysis demonstrates that female naive cells exhibit an X chromosome signature of the human preimplantation embryo. However, when introduced into mouse embryos the naive cells failed to efficiently generate interspecies chimeras. Our work provides a set of molecular benchmarks for evaluating the developmental identity of distinct human pluripotent states captured in vitro.

2016-08-16 | GSE85708 | GEO

Reproduction of reset cell

Project description:Functional-assay limitations are an emerging issue in characterizing human pluripotent stem cells (hPSCs). With rodent PSCs, chimera formation, using pre-implantation embryos, is the gold-standard assay of pluripotency. In hPSCs, this can only be monitored via teratoma formation or in vitro differentiation, as ethical concerns preclude generation of human-animal chimera. To circumvent this issue, we established a functional assay utilizing interspecific blastocyst injection and in vitro culture (interspecies in vitro chimera assay). The assay uses mouse pre-implantation embryos and human PSCs to make interspecies chimeras cultured in vitro to the early egg cylinder stage. When hiPSCs, both conventional and naive type, which called “reset cell”, were injected into mouse embryos and cultured. The cells were never integrated into the epiblast of egg cylinder stage-embryo. These results suggest that hPSCs, including naïve type, are unable to form chimera with mouse embryo.

2015-03-10 | GSE66657 | GEO

Reproduction of reset cell

Project description:Functional-assay limitations are an emerging issue in characterizing human pluripotent stem cells (hPSCs). With rodent PSCs, chimera formation, using pre-implantation embryos, is the gold-standard assay of pluripotency. In hPSCs, this can only be monitored via teratoma formation or in vitro differentiation, as ethical concerns preclude generation of human-animal chimera. To circumvent this issue, we established a functional assay utilizing interspecific blastocyst injection and in vitro culture (interspecies in vitro chimera assay). The assay uses mouse pre-implantation embryos and human PSCs to make interspecies chimeras cultured in vitro to the early egg cylinder stage. When hiPSCs, both conventional and naive type, which called M-bM-^@M-^\reset cellM-bM-^@M-^], were injected into mouse embryos and cultured. The cells were never integrated into the epiblast of egg cylinder stage-embryo. These results suggest that hPSCs, including naM-CM-/ve type, are unable to form chimera with mouse embryo. Reset cells were converted from conventional human iPSC line PB004, and then compared their gene expression profile with or without transgene overexpression induced by doxycyclin treatment.

2015-03-10 | E-GEOD-66657 | biostudies-arrayexpress

Temporal activation of NR5A2 and RARγ induce functional human naïve pluripotent state via modulating TGFβ pathway

Project description:Rejuvenated primed human pluripotent stem cells, naïve cells, are accessible through the manipulating transcription factors, singaling pathways or a combination of both. However, there is a notable challenge in the functions of naïve hPSCs. Here, we show that the brief treatment with two chemical agonists (2a) of nuclear receptors NR5A2 and RARγ along with 2i and lif (2a2iL) is sufficient to induce naive pluripotency during the reprogramming of fibroblasts and pre-established hPSCs as well as the generation of new cell lines from preimplantation embryos. These cells manifested global naive-specific critera especially the contribution into the human-mouse chimeras. We demonstrated that TGF-β pathway activity is potentially critical for induction and maintenance of 2a2iL naive hPSCs. Consequently, transient activation of TGF-β resulted in generation of naive hPSCs in 2iL condition. These results represent a naive pluripotent state which is in a top point of developmental potential equivalent with preimplantation human embryo.

2018-07-03 | GSE116501 | GEO

Protein expression landscape defines the formation potential of mouse blastoids from EPS cells

Project description:Preimplantation embryo development is a precisely regulated process organized by maternally inherited and newly synthesized proteins. Recently, some studies have reported that blastocyst-like structures, named blastoids, can be generated from mouse ESCs (embryonic stem cells) or EPSCs (extended pluripotent stem cells). In this study, to explore the dynamic expression characteristics of proteins and their PTMs in mouse EPS blastoids, we revealed the protein expression profile of EPS-blastoids and metabolite characteristics by TMT-based quantitative mass spectrometry (MS) strategy. Furthermore, the protein phosphorylation sites were identified to show the phosphoproteomic analysis in blastoids compared with mouse early embryos. Above all, our study revealed the protein expression profile of EPS blastoids compared with mouse embryos during preimplantation development and indicated that glucose metabolism is key to blastoid formation.

2022-04-04 | PXD031002 | Pride

Naive Pluripotent Stem Cells Display Transcriptional and Epigenetic Signatures of the Human Pre-Implantation Embryo

Project description:Significant interest has been devoted to the isolation of human pluripotent stem cells displaying the naive state of mouse embryonic stem cells. However, to what extent naive human cells isolated in culture resemble pluripotent cells in vivo remains unclear. Here we present three lines of evidence indicating that naive pluripotent stem cells generated in the absence of transgenes share defining molecular signatures with the human pre-implantation embryo. First, a comprehensive analysis of the transposcriptome reveals that naive human cells have a retroelement expression profile of human cleavage stage embryos. Second, base-resolution mapping of the DNA methylome in naive human cells reveals a genome-wide reduction in CpG and non-CpG methylation levels. Third, female naive cells exhibit an X chromosome status that is similar to that of the human blastocyst. Our work demonstrates that pluripotent stem cells with epigenomic hallmarks of the early human embryo can be directly captured in vitro. Examine the methylomes of 6 naÃ¯ve, 2 primed and 2 re-primed human embryonic stem cells

2016-07-18 | E-GEOD-75868 | biostudies-arrayexpress

Metabolic control of DNA methylation and imprinted gene expression in naive pluripotent cells

Project description:Naive pluripotent epiblast cells of the preimplantation murine embryo and their in vitro counterpart, embryonic stem (ES) cells, have the capacity to give rise to all cells of the adult. Such developmental plasticity is associated with global genome hypomethylation. It is unclear whether genome methylation is dynamically regulated only via differential expression of DNA methyltransferases (DNMTs) and Ten-eleven Translocation (TET) enzymes, which oxidase methylated DNA. Here we show that LIF/Stat3 signalling induces genomic hypomethylation via metabolic reconfiguration. In Stat3-/- ES cells we observed decreased alpha-ketoglutarate (ɑKG) production from reductive Glutamine metabolism, leading to decreased TET activity, increased Dnmt3a/b expression and to a global increase in DNA methylation. Notably, genome methylation is dynamically controlled by simply modulating αKG availability, mitochondrial activity or Stat3 activation in mitochondria, indicating effective crosstalk between metabolism and the epigenome. Stat3-/- ES cells also show increased methylation at Imprinting Control Regions accompanied with differential expression of >50% of imprinted genes. Single-cell transcriptome analysis of Stat3-/- embryos confirmed dysregulated expression of Dnmt3a/b, Tet2, and imprinted genes in vivo. Our results reveal that the LIF/Stat3 signal bridges the metabolic and epigenetic profiles of naive pluripotent cells, ultimately controlling genome methylation and imprinted gene expression. Several imprinted genes regulate cell proliferation and are often misregulated in tumors. Moreover, a wide range of cancers display Stat3-overactivation, raising the possibility that the molecular module we described here is exploited under pathological conditions.

2020-11-26 | PXD020385 | Pride

Cell competition as a barrier for interspecies chimerism between evolutionary distant species

Project description:we develop an interspecies pluripotent stem cell (PSC) co-culture strategy and uncover a previously unknown mode of cell competition. Interspecies PSC competition occurs during primed but not naive pluripotency, and between evolutionarily distant species. We identified genes related to NF-κB signaling pathways, among others, were upregulated in loser cells and genetic inactivation of RELA, a core component of canonical NF-κB pathway, could overcome interspecies PSC competition. We further showed that an upstream regulator of the NF-κB signaling, MYD88 innate immune signal transduction adaptor, was also involved in promoting loser PSC elimination. Suppressing interspecies PSC competition via genetic perturbation of MYD88 or P65 improved engraftment of human cells in early post-implantation mouse embryos. Our study discovers a new paradigm of cell competition and paves the way for studying evolutionarily conserved cell competition mechanisms during early mammalian development. Strategies developed here to overcome interspecies PSC competition may facilitate interspecies organogenesis between evolutionary distant species, including humans.

2020-12-31 | GSE142394 | GEO

Molecular Criteria for Defining the Naive Human Pluripotent State

Project description:Molecular Criteria for Defining the Naive Human Pluripotent State

| PRJNA305609 | ENA

Early cleavage of preimplantation embryos is regulated by tRNAGln-TTG-derived small RNAs present in mature spermatozoa

Project description:Sperm-derived tsRNAs could act as acquired epigenetic factors and contribute to offspring phenotypes. However, the roles of specific tsRNAs in early embryo development remain to be elucidated. Here, by using pigs as a research model, we probed the tsRNA dynamics during spermatogenesis and sperm maturation, and demonstrated the delivery of tsRNAs from semen-derived exosomes to spermatozoa. By microinjection of the antisense sequence into in vitro fertilized oocytes and subsequent single-cell RNA-sequencing of embryos, we identified a specific functional tsRNA group (Gln-TTGs) that participate in the early cleavage of porcine preimplantation embryos, probably by regulating cell cycle-associated genes. Thus, specific tsRNAs present in mature spermatozoa play significant roles during preimplantation embryo development.

2020-07-13 | PXD019054 | Pride

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