The origin of mouse extraembryonic endoderm stem cell lines

Mapping Intimacies ◽

10.1101/2021.12.27.474300 ◽

2021 ◽

Author(s):

Jiangwei Lin

Keyword(s):

Gene Expression ◽

Cell Lines ◽

Cell Lineage ◽

Preimplantation Embryos ◽

Visceral Endoderm ◽

Primitive Endoderm ◽

Cellular Origin ◽

Extraembryonic Endoderm ◽

Parietal Endoderm ◽

Stem Cell Lines

Mouse extraembryonic endoderm stem (XEN) cell lines can be derived from preimplantation embryos (pre-XEN) and postimplantation embryos (post-XEN). XEN cells share a gene expression profile and cell lineage potential with primitive endoderm (PrE) blastocysts. However, the cellular origin of XEN cells in embryos remains unclear. Here, we report that post-XEN cell lines are derived both from the extraembryonic endoderm and epiblasts of postimplantation embryos and that pre-XEN cell lines are derived both from PrE and epiblasts of blastocysts. Our strategy consisted of deriving post-XEN cells from clumps of epiblasts, parietal endoderm (PE) and visceral endoderm (VE) and deriving pre-XEN cell lines from single PrE and single epiblasts of blastocysts. Thus, XEN cell lines in the mouse embryo originate not only from PrE and PrE-derived lineages but also from epiblast and epiblast-derived lineages of blastocysts and postimplantation embryos.

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SOX17 Is Not Required for the Derivation and Maintenance of Mouse Extraembryonic Endoderm Stem Cell Lines

10.1101/2022.01.09.475525 ◽

2022 ◽

Author(s):

Xudong Dong ◽

Ailing Ding ◽

Jiangwei Lin

Keyword(s):

Stem Cell ◽

Cell Lines ◽

Embryonic Stem ◽

Cell Lineage ◽

Preimplantation Embryos ◽

Primitive Endoderm ◽

Extraembryonic Endoderm ◽

Gene Expression Analyses ◽

Stem Cell Lines

Extraembryonic endoderm stem (XEN) cell lines can be derived and maintained in vitro and reflect the primitive endoderm cell lineage. SOX17 is thought to be required for the derivation and maintenance of mouse XEN cell lines. Here we have re-evaluated this requirement for SOX17. We derived multiple SOX17-deficient XEN cell lines from preimplantation embryos of a SOX17-Cre knockout strain and chemically converted multiple SOX17-deficient embryonic stem cell lines into XEN cell lines by transient culturing with retinoic acid and Activin A. We confirmed the XEN profile of SOX17-deficient cell lines by immunofluorescence with various markers, by NanoString gene expression analyses, and by their contribution to the extraembryonic endoderm of chimeric embryos produced by injecting these cells into blastocysts. Thus, SOX17 is not required for the derivation and maintenance of XEN cell lines.

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Investigation of cell lineage and differentiation in the extraembryonic endoderm of the mouse embryo

Development ◽

10.1242/dev.68.1.175 ◽

1982 ◽

Vol 68 (1) ◽

pp. 175-198

Author(s):

R. L. Gardner

Keyword(s):

Inner Cell Mass ◽

Cell Mass ◽

Cell Lineage ◽

Early Embryo ◽

Visceral Endoderm ◽

Primitive Endoderm ◽

Developmental Potential ◽

Extraembryonic Endoderm ◽

Parietal Endoderm ◽

Endodermal Cells

The technique of injecting genetically labelled cells into blastocysts was used in an attempt to determine whether the parietal and visceral endoderm originate from the same or different cell populations in the early embryo. When the developmental potential of 5th day primitive ectoderm and primitive endoderm cells was compared thus, only the latter were found to colonize the extraembryonic endoderm. Furthermore, single primitive endoderm cells yielded unequivocal colonization of both the parietal and the visceral endoderm in a proportion of chimaeras. However, in the majority of primitive endodermal chimaeras, donor cells were detected in the parietal endoderm only, cases of exclusively visceral colonization being rare. Visceral endoderm cells from 6th and 7th day post-implantation embryos also exhibited a striking tendency to contribute exclusively to the parietal endoderm following blastocyst injection. The above findings lend no support to a recent proposal that parietal and visceral endoderm are derived from different populations of inner cell mass cells. Rather, they suggest that the two extraembryonic endoderm layers originate from a common pool of primitive endoderm cells whose direction of differentiation depends on their interactions with non-endodermal cells.

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Cell interactions and endoderm differentiation in cultured mouse embryos

Development ◽

10.1242/dev.62.1.379 ◽

1981 ◽

Vol 62 (1) ◽

pp. 379-394

Author(s):

Brigid L. M. Hogan ◽

Rita Tilly

Keyword(s):

Basement Membrane ◽

Mouse Embryo ◽

Cell Lineage ◽

Giant Cells ◽

Visceral Endoderm ◽

Extraembryonic Endoderm ◽

Type Iv ◽

The Matrix ◽

Parietal Endoderm

Morphological and biochemical evidence is presented that the visceral extraembryonic endoderm of the 6·5-day mouse embryo will differentiate into parietal endoderm when cultured in contact with extraembryonic ectoderm undergoing transition into trophoblast giant cells. Egg cylinders from 6·5-day embryos were dissected into embryonic and extraembryonic halves and cultured in suspension in vitro for up to 7 days. After 4 days, the endoderm cells of the extraembryonic fragments morphologically resemble parietal endoderm, are associated with a thick basement membrane and synthesize large amounts of the matrix proteins laminin and Type IV procollagen. A similar transition in phenotype is not seen in the endoderm of embryonic fragments, nor in visceral extraembryonic endoderm cells cultured in isolation. In another series of experiments, complete egg cylinders were dissected free of visceral endoderm ovei lying the extraembryonic ectoderm and then cultured in vitro. The visceral endoderm cells which recolonize the surface of the extraembryonic ectoderm develop a parietal endoderm phenotype and lay down a thick basement membrane. These results suggest that the differentiation of the extraembryonic endoderm of the early mouse embryo into visceral and parietal phenotypes can be influenced by local cell—cell or cell—substrate interactions, and is not determined solely by cell lineage.

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Faculty Opinions recommendation of Gene expression signatures of seven individual human embryonic stem cell lines.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1027396.328522 ◽

2005 ◽

Author(s):

Renee Reijo Pera

Keyword(s):

Gene Expression ◽

Stem Cell ◽

Embryonic Stem Cell ◽

Cell Lines ◽

Human Embryonic Stem Cell ◽

Embryonic Stem ◽

Gene Expression Signatures ◽

Stem Cell Lines ◽

Individual Human

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An in situ cell marker for clonal analysis of development of the extraembryonic endoderm in the mouse*

Development ◽

10.1242/dev.80.1.251 ◽

1984 ◽

Vol 80 (1) ◽

pp. 251-288

Author(s):

R. L. Gardner

Keyword(s):

Enzyme Activity ◽

Malic Enzyme ◽

Cell Mass ◽

Differential Staining ◽

Wild Type ◽

Primitive Endoderm ◽

Extraembryonic Endoderm ◽

Blue Tetrazolium ◽

Malic Enzyme Activity ◽

Parietal Endoderm

Conditions were found for staining whole mid-gestation capsular parietal endoderms and visceral yolk sacs for malic enzyme activity that gave excellent discrimination between wildtype (Mod-1+/Mod-1+) cells and mutant (Mod-ln/Mod-1n) cells that lack the cytoplasmic form of the enzyme. Reciprocal blastocyst injection experiments were undertaken in which single primitive endoderm cells of one genotype were transplanted into embryos of the other genotype. In addition, Mod-1+/Mod-1+ early inner cell mass (ICM) cells were injected into Mod-1n/Mod-1n blastocysts, either in groups of two or three singletons or as daughter cell pairs. A substantial proportion of the resulting conceptuses showed mosaic histochemical staining in the parietal endoderm, visceral yolk sac, or in both these membranes. Stained cells were invariably intimately intermixed with unstained cells in the mosaic parietal endoderms. In contrast, one or both of two distinct patterns of staining could be discerned in mosaic visceral yolk sacs. The first, a conspicuously ‘coherent’ pattern, was found to be due to endodermal chimaerism; the second, a more diffuse pattern, was attributable to chimaerism in the mesodermal layer of this membrane. The overall distribution of cells with donor staining characteristics resulting from primitive endoderm versus early ICM cell injections was consistent with findings in earlier experiments in which allozymes of glucosephosphate isomerase were used as markers. The conspicuous lack of phenotypically intermediate cells in predominantly stained areas of mosaic membranes suggested that the histochemical difference between Mod-1+/Mod-1+ and Mod-1n/Mod-ln genotypes was cell-autonomous. This conclusion was strengthened by the results of staining mixed in vitro cultures of parietal endoderm in which presence or absence of phagocytosed melanin granules was used as an independent means of distinguishing wild type from null cells. By substituting tetranitro blue tetrazolium for nitro blue tetrazolium in the incubation medium, satisfactory differential staining was obtained for both the extraembryonic endoderm and other tissues of earlier postimplantation wild type versus null embryos. Finally, absence of cytoplasmic malic enzyme activity does not appear to have a significant effect on the viability or behaviour of mutant cells.

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Reversible programming of pluripotent cell differentiation

Journal of Cell Science ◽

10.1242/jcs.113.3.555 ◽

2000 ◽

Vol 113 (3) ◽

pp. 555-566 ◽

Cited By ~ 9

Author(s):

J. Lake ◽

J. Rathjen ◽

J. Remiszewski ◽

P.D. Rathjen

Keyword(s):

Gene Expression ◽

Embryoid Bodies ◽

Visceral Endoderm ◽

Es Cell ◽

Primitive Endoderm ◽

Pluripotent Cell ◽

Pluripotent Cells ◽

Differentiation Potential

We have undertaken an in vitro differentiation analysis of two related, interconvertible, pluripotent cell populations, ES and early primitive ectoderm-like (EPL) cells, which are most similar in morphology, gene expression, cytokine responsiveness and differentiation potential in vivo to ICM and early primitive ectoderm, respectively. Pluripotent cells were differentiated in vitro as aggregates (embryoid bodies) and the appearance and abundance of cell lineages were assessed by morphology and gene expression. Differentiation in EPL cell embryoid bodies recapitulated normal developmental progression in vivo, but was advanced in comparison to ES cell embryoid bodies, with the rapid establishment of late primitive ectoderm specific gene expression, and subsequent loss of pluripotent cell markers. Nascent mesoderm was formed earlier and more extensively in EPL cell embryoid bodies, and resulted in the appearance of terminally differentiated mesodermal cell types prior to and at higher levels than in ES cell embryoid bodies. Nascent mesoderm in EPL cell embryoid bodies was not specified but could be programmed to alternative fates by the addition of exogenous factors. EPL cells remained competent to form primitive endoderm even though this is not the normal fate of primitive ectoderm in vivo. The establishment of primitive ectoderm-like gene expression and inability to participate in embryogenesis following blastocyst injection is therefore not directly associated with restriction in the ability to form extra-embryonic lineages. However, the EPL cell embryoid body environment did not support differentiation of primitive endoderm to visceral endoderm, indicating the lack of an inductive signal for visceral endoderm formation deduced to originate from the pluripotent cells. Similarly, the inability of EPL cells to form neurons when differentiated as embryoid bodies was attributable to perturbation of the differentiation environment and loss of inductive signals rather than a restricted differentiation potential. Reversion of EPL cells to ES cells was accompanied by restoration of ES cell-like differentiation potential. These results demonstrate the ability of pluripotent cells to adopt developmentally distinct, stable cell states with altered differentiation potentials.

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