analysis of alternative signaling pathways of endoderm induction of human embryonic stem cells identifies context specific differences分析内胚层的替代信号通路诱导人类胚胎干细胞识别上下文特定的差异.pdfVIP

Mathew et al. BMC Systems Biology 2012, 6:154 /1752-0509/6/154 RESEARCH ARTICLE Open Access Analysis of alternative signaling pathways of endoderm induction of human embryonic stem cells identifies context specific differences 1 2 3 1 4,5,6,7 1,2* Shibin Mathew , Maria Jaramillo , Xinan Zhang , Li Ang Zhang , Alejandro Soto-Gutiérrez and Ipsita Banerjee Abstract Background: Lineage specific differentiation of human embryonic stem cells (hESCs) is largely mediated by specific growth factors and extracellular matrix molecules. Growth factors initiate a cascade of signals which control gene transcription and cell fate specification. There is a lot of interest in inducing hESCs to an endoderm fate which serves as a pathway towards more functional cell types like the pancreatic cells. Research over the past decade has established several robust pathways for deriving endoderm from hESCs, with the capability of further maturation. However, in our experience, the functional maturity of these endoderm derivatives, specifically to pancreatic lineage, largely depends on specific pathway of endoderm induction. Hence it will be of interest to understand the underlying mechanism mediating such induction and how it is translated to further maturation. In this work we analyze the regulatory interactions mediating different pathways of endoderm induction by identifying co-regulated transcription factors. Results: hESCs were induced towards endoderm using activin A and 4 different growth factors (FGF2 (F), BMP4 (B), PI3KI (P), and WNT3A (W)) and their combinations thereof, resulting in 15 total experimental conditions. At the end of differentiation each condition was analyzed by