کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2078088 1079769 2008 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
NANOG Is a Direct Target of TGFβ/Activin-Mediated SMAD Signaling in Human ESCs
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوتکنولوژی یا زیست‌فناوری
پیش نمایش صفحه اول مقاله
NANOG Is a Direct Target of TGFβ/Activin-Mediated SMAD Signaling in Human ESCs
چکیده انگلیسی

SummarySelf-renewal of human embryonic stem cells (ESCs) is promoted by FGF and TGFβ/Activin signaling, and differentiation is promoted by BMP signaling, but how these signals regulate genes critical to the maintenance of pluripotency has been unclear. Using a defined medium, we show here that both TGFβ and FGF signals synergize to inhibit BMP signaling; sustain expression of pluripotency-associated genes such as NANOG, OCT4, and SOX2; and promote long-term undifferentiated proliferation of human ESCs. We also show that both TGFβ- and BMP-responsive SMADs can bind with the NANOG proximal promoter. NANOG promoter activity is enhanced by TGFβ/Activin and FGF signaling and is decreased by BMP signaling. Mutation of putative SMAD binding elements reduces NANOG promoter activity to basal levels and makes NANOG unresponsive to BMP and TGFβ signaling. These results suggest that direct binding of TGFβ/Activin-responsive SMADs to the NANOG promoter plays an essential role in sustaining human ESC self-renewal.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 3, Issue 2, 7 August 2008, Pages 196–206
نویسندگان
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