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Ceramide in stem cell differentiation and embryo development: novel functions of a topological cell-signaling lipid and the concept of ceramide compartments.

Bieberich E - J Lipids (2010)

Bottom Line: In the last two decades, the view on the function of ceramide as a sole metabolic precursor for other sphingolipids has completely changed.A plethora of studies has shown that ceramide is an important lipid cell-signaling factor regulating apoptosis in a variety of cell types.Recent studies suggest that ceramide is a critical cell-signaling factor for stem cell differentiation and cell polarity, two processes at the core of embryo development.

View Article: PubMed Central - PubMed

Affiliation: Program in Developmental Neurobiology, Institute of Molecular Medicine and Genetics, School of Medicine, Medical College of Georgia, 1120 15th Street Room CA4012, Augusta, GA 30912, USA.

ABSTRACT
In the last two decades, the view on the function of ceramide as a sole metabolic precursor for other sphingolipids has completely changed. A plethora of studies has shown that ceramide is an important lipid cell-signaling factor regulating apoptosis in a variety of cell types. With the advent of new stem cell technologies and knockout mice for specific steps in ceramide biosynthesis, this view is about to change again. Recent studies suggest that ceramide is a critical cell-signaling factor for stem cell differentiation and cell polarity, two processes at the core of embryo development. This paper discusses studies on ceramide using in vitro differentiated stem cells, embryo cultures, and knockout mice with the goal of linking specific developmental stages to exciting and novel functions of this lipid. Particular attention is devoted to the concept of ceramide as a topological cell-signaling lipid: a lipid that forms distinct structures (membrane domains and vesicles termed "sphingosome"), which confines ceramide-induced cell signaling pathways to localized and even polarized compartments.

No MeSH data available.


Related in: MedlinePlus

Structure of ceramide and its derivatives. (a) Natural derivatives of ceramide. All of the sphingolipids are derived from the condensation reaction of serine with palmitoyl-CoA, which is followed by reduction, acylation, and desaturation reactions to yield ceramide. In addition to the derivatives shown, glucosyl- or galactosylceramide and ceramide-1-phosphate are important structural and cell-signaling lipids, in particular for myelin formation and inflammation. (b) Synthetic analog of ceramide. The polar serine head group is preserved in ceramide and many sphingolipid analogs (only one analog (S18) is shown here). This minimal structural motif is composed of two hydroxyl groups β-positioned to an amino group or an imino group, which is linked to a hydrocarbon chain (dashed box, S18 or N-oleyl serinol is a derivative of 2-amino 1,3-propanediol).
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fig1: Structure of ceramide and its derivatives. (a) Natural derivatives of ceramide. All of the sphingolipids are derived from the condensation reaction of serine with palmitoyl-CoA, which is followed by reduction, acylation, and desaturation reactions to yield ceramide. In addition to the derivatives shown, glucosyl- or galactosylceramide and ceramide-1-phosphate are important structural and cell-signaling lipids, in particular for myelin formation and inflammation. (b) Synthetic analog of ceramide. The polar serine head group is preserved in ceramide and many sphingolipid analogs (only one analog (S18) is shown here). This minimal structural motif is composed of two hydroxyl groups β-positioned to an amino group or an imino group, which is linked to a hydrocarbon chain (dashed box, S18 or N-oleyl serinol is a derivative of 2-amino 1,3-propanediol).

Mentions: Embryonic stem (ES) cells in vitro differentiated to neural cell types undergo phenotypical changes that recapitulate embryo development. In the first differentiation step called germ layer formation, nonpolarized stem cells form embryoid bodies that are composed of a two-layer sphere: an outer primitive endoderm and an inner primitive ectoderm layer [16]. Since the primitive ectoderm is the primordial epithelium for all embryonic tissues, embryoid bodies are a bona fide in vitro model for the acquisition of germ layer cell polarity. Apicobasal cell polarity of primitive ectoderm cells is crucial for the organization and morphogenesis of the three embryonic germ layers: endoderm, mesoderm, and ectoderm. When embryoid bodies were depleted of ceramide by the incubation with myriocin or fumonisin B1, they did not form a primitive ectoderm layer. Instead, massive apoptosis of cells within the embryoid bodies was observed [16]. Supplementation of the culture medium with C16 ceramide or the novel ceramide analog N-oleoyl serinol (S18) prevented apoptosis and restored primitive ectoderm formation (Figure 1 for structures). These intriguing results were the first experimental evidence that ceramide was functionally involved in the regulation of embryonic cell polarity.


Ceramide in stem cell differentiation and embryo development: novel functions of a topological cell-signaling lipid and the concept of ceramide compartments.

Bieberich E - J Lipids (2010)

Structure of ceramide and its derivatives. (a) Natural derivatives of ceramide. All of the sphingolipids are derived from the condensation reaction of serine with palmitoyl-CoA, which is followed by reduction, acylation, and desaturation reactions to yield ceramide. In addition to the derivatives shown, glucosyl- or galactosylceramide and ceramide-1-phosphate are important structural and cell-signaling lipids, in particular for myelin formation and inflammation. (b) Synthetic analog of ceramide. The polar serine head group is preserved in ceramide and many sphingolipid analogs (only one analog (S18) is shown here). This minimal structural motif is composed of two hydroxyl groups β-positioned to an amino group or an imino group, which is linked to a hydrocarbon chain (dashed box, S18 or N-oleyl serinol is a derivative of 2-amino 1,3-propanediol).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3066852&req=5

fig1: Structure of ceramide and its derivatives. (a) Natural derivatives of ceramide. All of the sphingolipids are derived from the condensation reaction of serine with palmitoyl-CoA, which is followed by reduction, acylation, and desaturation reactions to yield ceramide. In addition to the derivatives shown, glucosyl- or galactosylceramide and ceramide-1-phosphate are important structural and cell-signaling lipids, in particular for myelin formation and inflammation. (b) Synthetic analog of ceramide. The polar serine head group is preserved in ceramide and many sphingolipid analogs (only one analog (S18) is shown here). This minimal structural motif is composed of two hydroxyl groups β-positioned to an amino group or an imino group, which is linked to a hydrocarbon chain (dashed box, S18 or N-oleyl serinol is a derivative of 2-amino 1,3-propanediol).
Mentions: Embryonic stem (ES) cells in vitro differentiated to neural cell types undergo phenotypical changes that recapitulate embryo development. In the first differentiation step called germ layer formation, nonpolarized stem cells form embryoid bodies that are composed of a two-layer sphere: an outer primitive endoderm and an inner primitive ectoderm layer [16]. Since the primitive ectoderm is the primordial epithelium for all embryonic tissues, embryoid bodies are a bona fide in vitro model for the acquisition of germ layer cell polarity. Apicobasal cell polarity of primitive ectoderm cells is crucial for the organization and morphogenesis of the three embryonic germ layers: endoderm, mesoderm, and ectoderm. When embryoid bodies were depleted of ceramide by the incubation with myriocin or fumonisin B1, they did not form a primitive ectoderm layer. Instead, massive apoptosis of cells within the embryoid bodies was observed [16]. Supplementation of the culture medium with C16 ceramide or the novel ceramide analog N-oleoyl serinol (S18) prevented apoptosis and restored primitive ectoderm formation (Figure 1 for structures). These intriguing results were the first experimental evidence that ceramide was functionally involved in the regulation of embryonic cell polarity.

Bottom Line: In the last two decades, the view on the function of ceramide as a sole metabolic precursor for other sphingolipids has completely changed.A plethora of studies has shown that ceramide is an important lipid cell-signaling factor regulating apoptosis in a variety of cell types.Recent studies suggest that ceramide is a critical cell-signaling factor for stem cell differentiation and cell polarity, two processes at the core of embryo development.

View Article: PubMed Central - PubMed

Affiliation: Program in Developmental Neurobiology, Institute of Molecular Medicine and Genetics, School of Medicine, Medical College of Georgia, 1120 15th Street Room CA4012, Augusta, GA 30912, USA.

ABSTRACT
In the last two decades, the view on the function of ceramide as a sole metabolic precursor for other sphingolipids has completely changed. A plethora of studies has shown that ceramide is an important lipid cell-signaling factor regulating apoptosis in a variety of cell types. With the advent of new stem cell technologies and knockout mice for specific steps in ceramide biosynthesis, this view is about to change again. Recent studies suggest that ceramide is a critical cell-signaling factor for stem cell differentiation and cell polarity, two processes at the core of embryo development. This paper discusses studies on ceramide using in vitro differentiated stem cells, embryo cultures, and knockout mice with the goal of linking specific developmental stages to exciting and novel functions of this lipid. Particular attention is devoted to the concept of ceramide as a topological cell-signaling lipid: a lipid that forms distinct structures (membrane domains and vesicles termed "sphingosome"), which confines ceramide-induced cell signaling pathways to localized and even polarized compartments.

No MeSH data available.


Related in: MedlinePlus