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

ABSTRACT: 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.

OTHER RELATED OMICS DATASETS IN: PRJNA105499PRJNA99953PRJNA105501PRJNA105503

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE7902 | GEO | 2007/06/27

SECONDARY ACCESSION(S): PRJNA99953

REPOSITORIES: GEO

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Project description:Embryonic stem cells (ES cells) are pluripotent stem cells that can contribute to all lineages of the embryo proper and were first isolated in 1981 in this laboratory (Evans and Kaufmann, 1981). They have contributed immeasurably to biology, both in terms of studying pluripotent stem cell maintenance in culture and in vitro differentiation, and because they can be easily genetically manipulated in culture, allowing for the production of mice with designed specific mutations (targeted mice), via homologous recombination. The recent isolation of human ES cell lines is promising in terms of stem cell therapy development. Mouse ES cell lines are isolated from the inner cell masses of mouse blastocysts between days 3.5 and 5.0 post coitum, or from the inner cell masses of delayed blastocysts. However, it has been suggested that some aspects of their biology may be more similar to embryonic ectoderm from early post implantation embryos, than to pre-implantation blastocysts. It has also been suggested that human embryonic stem cells are more similar to mouse stem cells derived from early embryonic ectoderm, than to mouse ES cells. Until recently, however, it has been difficult to answer these questions definitively, as the quantity of tissue available from early embryos is extremely limiting. However, we have used two rounds of RNA amplification on early embryonic samples and individual colonies picked from ES cell culture to compare the transcriptomic profiles of mouse ES cells with the embryonic tissues from with these cells are commonly derived, and with slightly later embryonic stages. We have found that ES cells are notably most similar in profile to embryonic ectoderm at day 5.5 (EE5.5) . ES cells cannot be derived from this post implantation embryonic tissue, so this result is in some ways surprising. However, ES cells show key differences from EE5.5, including the expression of markers of pluripotency such as Oct4 and Nanog (see gene lists acompanying this record), which explain how their ability to contribute to all tissues of the embryo proper is retained. Keywords: cell type comparison

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

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