Characterization of a pluripotent stem cell line derived from a mouse embryo

Wobus, Anna M.; Holzhausen, H.-J.; Jäkel, P.; Schöneich, J.

doi:10.1016/0014-4827(84)90246-5

Cited by 273 publications

(156 citation statements)

References 11 publications

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“…It is well known that undifferentiated ES cells can form teratomas or teratocarcinomas (see ref. 37). Although Pax4 expression in ES cells resulted in up to 80% insulin-producing cells, remaining undifferentiated cells may still possess oncogenic properties.…”

Section: Discussionmentioning

confidence: 99%

Expression of Pax4 in embryonic stem cells promotes differentiation of nestin-positive progenitor and insulin-producing cells

Błyszczuk

Czyż

Kania

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Mouse embryonic stem (ES) cells differentiate into cells of all three primary germ layers including endodermal cells that produce insulin in vitro.We show that constitutive expression of Pax4 (Pax4 ؉ ), and to a lesser extent Pdx1 (Pdx1 ؉ ), affects the differentiation of ES cells and significantly promote the development of insulin-producing cells. In Pax4 overexpressing R1 ES cells, isl-1, ngn3, insulin, islet amyloid polypeptide, and glucose transporter 2 (Glut-2) mRNA levels increase significantly. The number of nestinexpressing (nestin؉) cells also increases. Constitutive Pax4 expression combined with selection of nestin؉ cells and histotypic culture conditions give rise to spheroids containing insulin-positive granules typical of embryonal and adult ␤ cells. In response to glucose, Pax4 ؉ and wild-type ES-derived cells release insulin. Transplantation of these cells into streptozotocin-treated diabetic mice results in a normalization of blood glucose levels. We conclude that constitutive expression of Pax4 in combination with histotypic cultivation facilitates ES cell differentiation into the pancreatic lineage, which leads to the formation of islet-like spheroid structures that produce increased levels of insulin.

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Section: Discussionmentioning

confidence: 99%

Expression of Pax4 in embryonic stem cells promotes differentiation of nestin-positive progenitor and insulin-producing cells

Błyszczuk

Czyż

Kania

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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408

322

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“…Among them, the alkaline phosphatase (AP) activity is a valuable marker for putative ES cells in mouse (Wobus et al, 1984) and other animals including fish, in which levels of AP activity are throughout the process similar to those of parental blastula cells ( Figure 3A; Wakamatsu et al, 1994;Bé jar et al, 1999;Chen et al, 2003a,b).…”

Section: Es Cell Technology In Fish Step By Stepmentioning

confidence: 99%

Fish ES Cells and Applications to Biotechnology

et al. 2006

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ES cells provide a promising tool for the generation of transgenic animals with site-directed mutations. When ES cells colonize germ cells in chimeras, transgenic animals with modified phenotypes are generated and used either for functional genomics studies or for improving productivity in commercial settings. Although the ES cell approach has been limited to mice, there is strong interest for developing the technology in fish. We describe the step-by-step procedure for developing ES cells in fish. Key aspects include avoiding cell differentiation, specific in vitro traits of pluripotency, and, most importantly, testing for production of chimeric animals as the main evidence of pluripotency. The entire process focuses on two model species, zebrafish and medaka, in which most work has been done. The achievements attained in these species, as well as their applicability to other commercial fish, are discussed. Because of the difficulties relating to germ line competence, mostly of long-term fish ES cells, alternative cell-based approaches such as primordial germ cells and nuclear transfer need to be considered. Although progress to date has been slow, there are promising achievements in homologous recombination and alternative avenues yet to be explored that can bring ES technology in fish to fruition.

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“…Under these conditions (Table 1), mES and mEG cells do not differentiate, maintain a relatively normal and stable karyotype and have an unlimited ability to self-renew [8,9]. Phenotypically, undifferentiated mES cells express specific cell surface markers like stage-specific embryonic antigen 1 (SSEA1) and membrane-bound receptors like gp130; possess enzyme activities for alkaline phosphatases, for telomerase, and express the epiblast/germ cell-restricted transcription factor Oct3/4 and the homeodomain protein Nanog [10][11][12][13][14][15][16], both of which are essential to maintain ES cell identity. Signal transduction and activator of transcription 3 (STAT3) [11], which is downstream of LIF activation, also plays an important accessory role in the maintenance of these cells in vitro [5].…”

Section: Embryonic Stem Cells Mousementioning

confidence: 99%

Embryonic stem cells and cardiomyocyte differentiation: phenotypic and molecular analyses

Wei

Juhász

et al. 2005

J Cellular Mol Med

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Heart disease and failure are often characterized by a loss of functioning cardiomyocytes, which are terminally differentiated and show a very limited capacity for regeneration. Cardiac transplantation is currently the treatment of choice for end-stage heart failure; however, the number of available donor organs limits this treatment option to a minority of patients [1]. The development of new therapeutic paradigms for heart failure and alternative thera- AbstractEmbryonic stem (ES) cell lines, derived from the inner cell mass (ICM) of blastocyst-stage embryos, are pluripotent and have a virtually unlimited capacity for self-renewal and differentiation into all cell types of an embryoproper. Both human and mouse ES cell lines are the subject of intensive investigation for potential applications in developmental biology and medicine. ES cells from both sources differentiate in vitro into cells of ecto-, endoand meso-dermal lineages, and robust cardiomyogenic differentiation is readily observed in spontaneously differentiating ES cells when cultured under appropriate conditions. Molecular, cellular and physiologic analyses demonstrate that ES cell-derived cardiomyocytes are functionally viable and that these cell derivatives exhibit characteristics typical of heart cells in early stages of cardiac development. Because terminal heart failure is characterized by a significant loss of cardiomyocytes, the use of human ES cell-derived progeny represents one possible source for cell transplantation therapies. With these issues in mind, this review will focus on the differentiation of pluripotent embryonic stem cells into cardiomyocytes as a developmental model, and the possible use of ES cell-derived cardiomyocytes as source of donor cells.

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Characterization of a pluripotent stem cell line derived from a mouse embryo

Cited by 273 publications

References 11 publications

Expression of Pax4 in embryonic stem cells promotes differentiation of nestin-positive progenitor and insulin-producing cells

Expression of Pax4 in embryonic stem cells promotes differentiation of nestin-positive progenitor and insulin-producing cells

Fish ES Cells and Applications to Biotechnology

Embryonic stem cells and cardiomyocyte differentiation: phenotypic and molecular analyses

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