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The growth factor environment defines distinct pluripotent ground states in novel blastocyst derived stem cells

ABSTRACT: Pluripotent stem cell lines can be derived from blastocyst embryos, which yield embryonic stem cell lines (ES cells), as well as the post-implantation epiblast, which gives rise to epiblast stem cell lines (EpiSCs). Remarkably, ES cells and EpiSCs display profound differences in the combination of growth factors that maintain their pluripotent state. Molecular and functional differences between these two stem cell types demonstrate that the tissue of origin and/or the growth factor milieu may be important determinants of the stem cell identity. We explored how developmental stage of the tissue of origin and culture growth factor conditions affect the stem cell pluripotent state. Our findings reveal that novel stem cell lines can be generated from blastocyst embryos with unique functional and molecular properties. We demonstrate that the culture growth factor environment and cell-cell interaction play a critical role in defining several unique and stable stem cell ground states. Keywords: Clonal analysis of FAB-SC gene expression

ORGANISM(S): Mus musculus

PROVIDER: GSE12519 | GEO | 2008/10/31

SECONDARY ACCESSION(S): PRJNA112917

REPOSITORIES: GEO

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The growth factor environment defines distinct pluripotent ground states in novel blastocyst derived stem cells

Project description:Pluripotent stem cell lines can be derived from blastocyst embryos, which yield embryonic stem cell lines (ES cells), as well as the post-implantation epiblast, which gives rise to epiblast stem cell lines (EpiSCs). Remarkably, ES cells and EpiSCs display profound differences in the combination of growth factors that maintain their pluripotent state. Molecular and functional differences between these two stem cell types demonstrate that the tissue of origin and/or the growth factor milieu may be important determinants of the stem cell identity. We explored how developmental stage of the tissue of origin and culture growth factor conditions affect the stem cell pluripotent state. Our findings reveal that novel stem cell lines can be generated from blastocyst embryos with unique functional and molecular properties. We demonstrate that the culture growth factor environment and cell-cell interaction play a critical role in defining several unique and stable stem cell ground states. Keywords: Clonal analysis of FAB-SC gene expression Cell type characterization - 3 separate single cell clones

2010-05-17 | E-GEOD-12519 | biostudies-arrayexpress

Sox2 Levels Define Pluripotent Ground States and Reprogramming Potential

Project description:Pluripotent stem cell lines derived from embryos of different stages have distinct pluripotent ground states, but similar levels of the transcription factor Oct4. Epiblast-derived pluripotent stem cells (EpiSCs), in contrast to embryonic stem (ES) cells, cannot form chimeras. We show that EpiSCs express lower levels of the transcription factors Sox2 and Klf4 than ES cells and have limited reprogramming potential, as shown by cell fusion. Sox2 overexpression dramatically increases the reprogramming potential, chimera formation, and germline contribution of EpiSCs. Therefore, although Oct4 is essential for reprogramming, the level of Sox2 defines both the reprogramming capability and the pluripotent ground states.

2010-12-31 | GSE15358 | GEO

Gene expression in undifferentiated human ES cells - Agilent

Project description:The application of human embryonic stem (ES) cells in medicine and biology has an inherent reliance on understanding the starting cell population. Human ES cells differ from mouse ES cells and the specific embryonic origin of both cell types is unclear. Previous work suggested that mouse ES cells could only be obtained from the embryo before implantation in the uterus1â5. Here we show that cell lines can be derived from the epiblast, a tissue of the postimplantation embryo that generates the embryo proper. These cells, which we refer to as EpiSCs (post-implantation epiblastderived ES cells), express transcription factors known to regulate pluripotency, maintain their genomic integrity, and robustly differentiate into the major somatic cell types as well as primordial germ cells. The EpiSC lines are distinct from mouse ES cells in their epigenetic state and the signals controlling their differentiation. Furthermore, EpiSC and human ES cells share patterns of gene expression and signalling responses that normally function in the epiblast. These results show that epiblast cells can be maintained as stable cell lines and interrogated to understand how pluripotent cells generate distinct fates during early development. *Note: EpiSCs were previously referred to as post-ES cells Keywords: cell type comparison 3 biological replicates of human ES cells were compared to mouse ES cells and EpiSCs.

2010-06-10 | E-GEOD-7900 | biostudies-arrayexpress

Transcription profiling of mouse ES cells and EpiSCs

Project description:The application of human embryonic stem (ES) cells in medicine; and biology has an inherent reliance on understanding the starting; cell population. Human ES cells differ from mouse ES cells and the; specific embryonic origin of both cell types is unclear. Previous; work suggested that mouse ES cells could only be obtained from; the embryo before implantation in the uterus1â5. Here we show; that cell lines can be derived from the epiblast, a tissue of the postimplantation; embryo that generates the embryo proper. These; cells, which we refer to as EpiSCs (post-implantation epiblastderived; ES cells), express transcription factors known to regulate; pluripotency, maintain their genomic integrity, and robustly differentiate; into the major somatic cell types as well as primordial; germ cells. The EpiSC lines are distinct from mouse ES cells in; their epigenetic state and the signals controlling their differentiation. Furthermore, EpiSC and human ES cells share patterns of; gene expression and signalling responses that normally function; in the epiblast. These results show that epiblast cells can be maintained; as stable cell lines and interrogated to understand how; pluripotent cells generate distinct fates during early development. *Note: EpiSCs were previously referred to as post-ES cells Experiment Overall Design: 3 biological replicates of each cell type (EpiSC and mouse ES) were compared.

2008-06-19 | E-GEOD-7866 | biostudies-arrayexpress

Capture of mouse and human stem cells with features of formative pluripotency [mouse, RNA-Seq 2]

Project description:Pluripotent cells emerge as a naïve founder population in the blastocyst, acquire capacity for germline and soma formation, and then undergo lineage priming. Mouse embryonic stem (ES) cells and epiblast stem cells (EpiSCs) respectively represent the initial naïve and final primed phases of pluripotency. Here we investigated the intermediate formative stage. Using minimal exposure to specification cues, we derived stem cells from formative mouse epiblast. Unlike ES cells or EpiSCs, formative stem (FS) cells responded directly to germ cell induction. They colonised somatic tissues and germline in chimaeras. Whole transcriptome analyses showed similarity to pre-gastrulation formative epiblast. Signal responsiveness and chromatin accessibility features reflect lineage capacitation. Furthermore, FS cells showed distinct transcription factor dependencies, relying critically on Otx2. Finally, FS cell culture conditions applied to human naïve cells or embryos supported expansion of similar stem cells, consistent with a conserved staging post on the trajectory of mammalian pluripotency.

2020-12-04 | GSE131555 | GEO

Capture of mouse and human stem cells with features of formative pluripotency [mouse, RNA-Seq 1]

2020-12-04 | GSE131553 | GEO

Capture of mouse and human stem cells with features of formative pluripotency [human, RNA-seq]

2020-12-04 | GSE131551 | GEO

Capture of mouse and human stem cells with features of formative pluripotency [ATAC-Seq]

2020-12-04 | GSE131549 | GEO

Novel cell lines from mouse epiblast share defining features with human embryonic stem cells

Project description:The application of human embryonic stem (ES) cells has an inherent reliance on understanding the starting cell population. Human ES cells differ from mouse ES cells and the specific embryonic origin of both cell types is unclear. Previous work suggested that mouse ES cells could only be obtained from the embryo prior to implantation in the uterus. Here we show that cell lines can be derived from the epiblast, a tissue of the post-implantation embryo that generates the embryo proper. These cells, which we refer to as EpiSCs (post-implantation epiblast-derived stem cells), express transcription factors known to regulate pluripotency, maintain their genomic integrity, and robustly differentiate into the major somatic cell types as well as primordial germ cells (PGCs). The post-ES cell lines are distinct from mouse ES cells in their epigenetic state and the signals controlling their differentiation. Furthermore, post-ES and human ES cells share patterns of gene expression and signalling responses that normally function in the epiblast. These results show that epiblast cells can be maintained as stable cell lines and interrogated to understand how pluripotent cells generate distinct fates during early development. This SuperSeries is composed of the SubSeries listed below.

2007-06-27 | GSE7902 | GEO

Gene expression in undifferentiated human ES cells - Agilent

Project description:The application of human embryonic stem (ES) cells in medicine and biology has an inherent reliance on understanding the starting cell population. Human ES cells differ from mouse ES cells and the specific embryonic origin of both cell types is unclear. Previous work suggested that mouse ES cells could only be obtained from the embryo before implantation in the uterus1–5. Here we show that cell lines can be derived from the epiblast, a tissue of the postimplantation embryo that generates the embryo proper. These cells, which we refer to as EpiSCs (post-implantation epiblastderived ES cells), express transcription factors known to regulate pluripotency, maintain their genomic integrity, and robustly differentiate into the major somatic cell types as well as primordial germ cells. The EpiSC lines are distinct from mouse ES cells in their epigenetic state and the signals controlling their differentiation. Furthermore, EpiSC and human ES cells share patterns of gene expression and signalling responses that normally function in the epiblast. These results show that epiblast cells can be maintained as stable cell lines and interrogated to understand how pluripotent cells generate distinct fates during early development. *Note: EpiSCs were previously referred to as post-ES cells Keywords: cell type comparison

2007-06-27 | GSE7900 | GEO

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