be230cLecture5

Formajon of germ layers ectoderm mesoderm and

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Unformatted text preview: for Directed DifferenJaJon Human ESCs or iPSCs Ventricular Cardiomyocytes •  ESC/iPSC cardiogenesis recapitulates the normal developmental program of the embryo •  Therefore, understand and reproduce the developmental program in vitro 3 4/15/13 Stepwise Cardiac Development, from Pluripotency to BeaJng Heart •  Summary: 1.  FormaJon of germ layers: ectoderm, mesoderm and endoderm 2.  Induce cardiogenic mesoderm 3.  DifferenJate cardiac cell types, principally cardiomyocytes, vascular smooth muscle and endothelial cells •  These early specificaJon events occur during the first 3 weeks of human gestaJon •  They occur concomitant with organizaJon of the overall body plan and specificaJon of different Jssues and organs •  Many of the signals have been established, and protocols exist for the commercial producJon of human cardiomyocytes from ESCs and iPSCs Early Cardiac Developmental Anatomy Stepwise Cardiac Development, from Pluripotency to BeaJng Heart •  Summary: 1.  2.  3.  •  •  •  FormaJon of germ layers: ectoderm, mesoderm and endoderm Induce cardiogenic mesoderm DifferenJate cardiac cell types, principally cardiomyocytes, vascular smooth muscle and endothelial cells These early specificaJon events occur during the first 3 weeks of human gestaJon They occur concomitant with organizaJon of the overall body plan and specificaJon of different Jssues and organs Many of the signals have been established, and protocols exist for the commercial producJon of human cardiomyocytes from ESCs and iPSCs 4 4/15/13 SegregaJon of Germ Layers: FormaJon of Mesoderm as DisJnct from Ectoderm and Endoderm Mesoderm ­ and Endoderm ­Inducing Signals •  •  •  •  Nodal and Transforming Growth Factor ­β (TGFβ) are most important inducers, in the embryo and also the principal factor used to iniJate mesendoderm formaJon in ESCs Receptor tyrosine kinase (RTK) signaling, e.g. FGF Wnt signaling The same factors operate in stem cell cultures as in embryos The inducJve signals emanate primarily from primiJve endoderm and induce mesenchymal cells  ­ the definiJve mes/endoderm  ­ to form from a furrow in the epiblast known as the primiJve The Persistence and Dose of Nodal/ TGFβ Specifies Cardiogenic Mesoderm Early streak Anterior Mes/endoderm Epiblast/ ESCs/iPSCs Later streak Anterior Endoderm Head Mesoderm Cardiac Anterior Mesoderm Posterior Ectoderm Body Mesoderm Posterior Posterior 5 4/15/13 The Persistence and Dose of Nodal/ TGFβ Spe...
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This document was uploaded on 04/09/2014.

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