Functional immobilization of signaling proteins enables control of stem cell fate

Functional immobilization of signaling proteins enables control of stem cell fate
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DOI:
10.1038/nmeth.1222
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发表时间:
2008-07-01
期刊:
影响因子:
48
通讯作者:
Zandstra, Peter W.
Zandstra, Peter W.
中科院分区:
生物学1区
文献类型:
--
作者:
Alberti, Kristin;Davey, Ryan E.;Zandstra, Peter W.

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配体的呈现方式在组织细胞整个发育过程中的命运中起着基础性的作用。我们报告了一种快速而简单的方法,将信号配体固定到马来酸酐共聚物薄膜涂层上,使信号配体能够在定义的浓度下稳定地呈现在界面上。我们使用白血病抑制因子(LIF)和干细胞因子(SCF)演示了这一平台技术的实用性。固定化的LIF支持小鼠胚胎干细胞(MESC)在没有添加扩散性LIF的情况下至少2周的多能性。LIF激活的信号转导和转录激活子3(STAT3)和丝裂原激活的蛋白激酶(MAPK)信号以剂量依赖的方式固定。介绍的方法允许对界面固定配体的细胞命运反应进行稳健的研究。
The mode of ligand presentation has a fundamental role in organizing cell fate throughout development. We report a rapid and simple approach for immobilizing signaling ligands to maleic anhydride copolymer thin-film coatings, enabling stable signaling ligand presentation at interfaces at defined concentrations. We demonstrate the utility of this platform technology using leukemia inhibitory factor (LIF) and stem cell factor (SCF). Immobilized LIF supported mouse embryonic stem cell (mESC) pluripotency for at least 2 weeks in the absence of added diffusible LIF. Immobilized LIF activated signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase (MAPK) signaling in a dose-dependent manner. The introduced method allows for the robust investigation of cell fate responses from interface-immobilized ligands.