Paracrine promotion of cardiomyogenesis in embryoid bodies by LIF modulated endoderm

Bader, Alice; Gruss, Astrid; Höllrigl, Alexandra; Al-Dubai, Haifa; Capetanaki, Yassemie; Weitzer, Georg

doi:10.1046/j.1432-0436.2001.068001031.x

Cited by 49 publications

(71 citation statements)

References 66 publications

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“…The inductive characteristic of the endoderm has been attributed to TGF-β superfamily and FGF family growth factors that have been reported to be involved in cardiac differentiation (Sugi and Lough 1994;Schultheiss, Xydas et al 1995;Sugi and Lough 1995;Schultheiss, Burch et al 1997;Schultheiss and Lassar 1997). It has been shown using mouse (m)ESCs that inhibition of primitive endoderm with diffusible leukemia inhibitory factor (LIF) during cell aggregation attenuates cardiomyocyte differentiation and that cardiomyogenesis could be rescued with parietal endoderm conditioned medium (Bader, Gruss et al 2001), suggesting that the primitive endoderm secretes factors that contribute to cardiac commitment in a paracrine, LIF independent manner. In mESC aggregates generated by mixing different ratios of Dox-inducible GATA4 overexpressing mESCs with the untransfected parental cell line (Holtzinger, Rosenfeld et al 2010), GATA4 overexpressing cells develop into SOX17 + cells that secrete BMPs and DKK to promote cardiac induction in the non-GATA4 overexpressing cells.…”

Section: Discussionmentioning

confidence: 99%

“…During embryonic development, precardiac mesoderm is in close contact with endoderm tissue which has been shown to play an inductive role as evidenced by the generation of beating cardiac tissue in cocultures of non-cardiogenic embryonic tissue explants and endodermal tissue (Orts Llorca 1963;Jacobson and Duncan 1968;Sugi and Lough 1994;Nascone and Mercola 1995;Schultheiss, Xydas et al 1995). In differentiating PSCs, ExE and its derivatives, visceral and parietal endoderm, have also been shown to promote cardiomyocyte differentiation in co-culture and conditioned medium studies (Hogan, Taylor et al 1981;Bader, Gruss et al 2001;Mummery, Ward-van Oostwaard et al 2003;Passier and Mummery 2005;Passier, Oostwaard et al 2005;Bin, Sheng et al 2006;Xu, Graichen et al 2008).…”

Section: Introductionmentioning

confidence: 99%

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Geometric Control of Cardiomyogenic Induction in Human Pluripotent Stem Cells

Bauwens

Song

Thavandiran

et al. 2011

Tissue Engineering Part A

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Pluripotent stem cells provide the opportunity to study human cardiogenesis in vitro, and are a renewable source of tissue for drug testing and disease models, including replacement cardiomyocytes that may be a useful treatment for heart failure. Typically, differentiation is initiated by forming spherical cell aggregates wherein an extraembryonic endoderm (ExE) layer develops on the surface. Given that interactions between endoderm and mesoderm influence embryonic cardiogenesis, we examined the impact of human embryonic stem cell (hESC) aggregate size on endoderm and cardiac development. We first demonstrated aggregate size control by micropatterning hESC colonies at defined diameters and transferring the colonies to suspension. The ratio of endoderm (GATA-6) to neural (PAX6) gene and protein expression increased with decreasing colony size. Subsequently, maximum mesoderm and cardiac induction occurred in larger aggregates when initiated with endoderm-biased hESCs (high GATA-6:PAX6), and in smaller aggregates when initiated with neural-biased hESCs (low GATA-6:PAX6). Additionally, incorporating micropatterned aggregates in a stirred suspension bioreactor increased cell yields and contracting aggregate frequency. We next interrogated the relationship between aggregate size and endoderm and cardiac differentiation efficiency in sizecontrolled aggregates, generated using forced aggregation, in defined cardiogenic medium.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Geometric Control of Cardiomyogenic Induction in Human Pluripotent Stem Cells

Bauwens

Song

Thavandiran

et al. 2011

Tissue Engineering Part A

View full text Add to dashboard Cite

show abstract

“…The IRESlacZHygro cassette was adapted from IRESCreHygro (Stanley et al, 2002). Embryoid body (EB) culture was adapted from the hanging drop method (Bader et al, 2001). GFP expression was analysed on a FACSCalibur (BD Biosciences).…”

Section: Es Cells and Gene Targetingmentioning

confidence: 99%

A tyrosine-rich domain within homeodomain transcription factor Nkx2-5 is an essential element in the early cardiac transcriptional regulatory machinery

et al. 2006

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Homeodomain factor Nkx2-5 is a central component of the transcription factor network that guides cardiac development; in humans, mutations in NKX2.5 lead to congenital heart disease (CHD). We have genetically defined a novel conserved tyrosine-rich domain (YRD) within Nkx2-5 that has co-evolved with its homeodomain. Mutation of the YRD did not affect DNA binding and only slightly diminished transcriptional activity of Nkx2-5 in a context-specific manner in vitro. However, the YRD was absolutely essential for the function of Nkx2-5 in cardiogenesis during ES cell differentiation and in the developing embryo. Furthermore, heterozygous mutation of all nine tyrosines to alanine created an allele with a strong dominant-negative-like activity in vivo: ES cell}embryo chimaeras bearing the heterozygous mutation died before term with cardiac malformations similar to the more severe anomalies seen in NKX2.5 mutant families. These studies suggest a functional interdependence between the NK2 class homeodomain and YRD in cardiac development and evolution, and establish a new model for analysis of Nkx2-5 function in CHD.

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“…It also indirectly influences cardiomyogenesis in mES cell cultures through its effects on parietal endoderm differentiation [47,48]. By altering in the forming EB the relative content of other cell lineages (e.g., endoderm) that provided cardiomyogenic-inducing factors, the differentiation potential of ES cells to form CMs will be adversely affected.…”

Section: Induction Of Embryonic Stem Cells To Form Cardiomyocytes In mentioning

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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Paracrine promotion of cardiomyogenesis in embryoid bodies by LIF modulated endoderm

Cited by 49 publications

References 66 publications

Geometric Control of Cardiomyogenic Induction in Human Pluripotent Stem Cells

Geometric Control of Cardiomyogenic Induction in Human Pluripotent Stem Cells

A tyrosine-rich domain within homeodomain transcription factor Nkx2-5 is an essential element in the early cardiac transcriptional regulatory machinery

Embryonic stem cells and cardiomyocyte differentiation: phenotypic and molecular analyses

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