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Cell Journal، جلد ۱۵، شماره Suppl ۱، صفحات ۱۹-۱۹
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عنوان انگلیسی Os-17: Small Molecule Induction of Human Embryonic Stem Cells Towards Definitive Endoderm
چکیده انگلیسی مقاله Objective: Definitive endoderm (DE) formation is the most important stage that all endodermal organs pass through during their development. So, in vitro production of definitive endoderm is one of the important issues in stem cell related differentiation studies and can help to efficiently produce endoderm derivatives for therapeutic applications. Despite the enormous progress in studying definitive endoderm (DE) differentiation from human embryonic stem cells (hESCs), none of the reported protocols have produced a universal, cost-effective, and competent DE with the capability to further differentiate into endodermal derivatives. Materials and Methods: In this study, by using a twostep differentiation strategy, we have treated hESCs for one day with “priming” small molecules (SM), [stauprimide, NSC-308848, rapamycin (Rapa), and/or CHIR] and for the next three days with “inducing” SM (LY294002, cymarin, IDE1 and/or IDE2) in conjunction with activin A. In the positive control group, we treated hESCs with Wnt3a (25 ng/ml) for one day and activin A (100 ng/ml; W/A100-A100) for the next three days. Results: Gene expression analysis showed that treatment of hESCs with 100 nM Rapa and 50 ng/ml activin A (Rapa-A50) out of 25 combinations of factors gave rise to higher expressions of two DE-specific genes, SOX17 and FOXA2. Similar results were obtained after treating two other hESC lines with this regimen. To investigate the competency of Rapa-A50-induced DE for further differentiation into endodermal derivatives, these cells and W/A100-A100-induced DE cells (positive control) were further differentiated into pancreatic progenitors (PP), then into pancreatic endocrine (PE) cells using five previously described differentiation protocols. Gene analysis of differentiated cells showed that the established protocols were insufficient to enable universal differentiation into PE, whereas Rapa-A50-induced DE cells were more competent for PP differentiation in a protocol-dependent manner. Additionally, Rapa-A50-induced DE had the capability to differentiate into hepatocyte-like cells (HLCs) as efficiently as W/A100-A100-induced DE. Conclusion: These data have indicated that hESCs primed with Rapa, and induced by a lower concentration of activin A, could lead to DE that had the capability to further differentiate into HLCs and PP cells, but not PE cells. Thus, current protocols for the differentiation of DE into PE still need additional study.
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نشانی اینترنتی http://celljournal.org/journal/article/abstract/804
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