Molecular Criteria for Defining the Naive Human Pluripotent State
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ABSTRACT:
PROVIDER: PRJNA305609 | ENA |
REPOSITORIES: ENA
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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.
2016-07-18 | GSE75868 | GEO
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
Project description:Recent studies have aimed to convert cultured human pluripotent cells to a naive state, but it remains unclear to what extent the resulting cells recapitulate in vivo naive pluripotency. Here we propose a set of molecular criteria for evaluating the naive human pluripotent state by comparing it to the human embryo. We show that transcription of transposable elements provides a sensitive measure of the concordance between pluripotent stem cells and early human development. We also show that induction of the naive state is accompanied by genome-wide DNA hypomethylation, which is reversible except at imprinted genes, and that the X chromosome status resembles that of the human preimplantation embryo. However, we did not see efficient incorporation of naive human cells into mouse embryos. Overall, the different naive conditions we tested showed varied relationships to human embryonic states based on molecular criteria, providing a backdrop for future analysis of naive human pluripotency.
| S-EPMC5065525 | biostudies-literature
Project description:Totipotency is the ability of a single cell to give rise to all the differentiated cells that build the conceptus, yet how to capture this property in vitro remains incompletely understood. Defining totipotency relies upon a variety of assays of variable stringency. Here we describe criteria to define totipotency. We illustrate how distinct criteria of increasing stringency can be used to judge totipotency by evaluating candidate totipotent cell types in the mouse, including early blastomeres and expanded or extended pluripotent stem cells. Our data challenge the notion that expanded or extended pluripotent states harbor increased totipotent potential relative to conventional embryonic stem cells under in vivo conditions.
2020-10-13 | GSE145609 | GEO
Project description:Defining totipotency using criteria of increasing stringency
| PRJNA607734 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-08-16 | E-GEOD-85708 | biostudies-arrayexpress
Project description:Molecular Criteria for Defining the Naive Human Pluripotent State [methylation profiling]
| PRJNA339143 | ENA
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 naïve, 2 primed and 2 re-primed human embryonic stem cells
2016-07-18 | E-GEOD-75868 | biostudies-arrayexpress
Project description:Here we propose a set of molecular criteria for evaluating the naive human pluripotent state. We show by RNA-seq that transcription of transposable elements provides a sensitive measure of the concordance between pluripotent stem cells and early human development. RNA-seq of 4 naive ES samples in 4i/LA, 3 naive ES samples in 5i/LA, 2 transgene-dependant naive ES cell samples, and 5 primed ES cell samples (in hESM)
2016-07-15 | E-GEOD-83765 | biostudies-arrayexpress
Project description:Here we propose a set of molecular criteria for evaluating the naive human pluripotent state. We show by RNA-seq that transcription of transposable elements provides a sensitive measure of the concordance between pluripotent stem cells and early human development. RNA-seq of 3 naive ES samples in NHSM (Gafni et al.) and 3 primed ES cell samples (in hESM)
2016-08-16 | E-GEOD-85689 | biostudies-arrayexpress