Defined three-dimensional microenvironments boost induction of pluripotency
Defined three-dimensional microenvironments boost induction of pluripotency
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DOI：
10.1038/nmat4536
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发表时间：
2016-03-01
期刊：
影响因子：
41.2
通讯作者：
Lutolf, Matthias P.
中科院分区：
文献类型：
--
作者：
Caiazzo, Massimiliano;Okawa, Yuya;Lutolf, Matthias P.
自从发现诱导多能干细胞（iPSC）以来，已经探索了许多方法来改进基于二维（2D）细胞培养系统的原始方案。令人惊讶的是，对于生物学上更忠实的3D环境对体细胞重编程的影响一无所知。在这里，我们报告了一个系统的分析体细胞的重编程如何发生在工程化的3D细胞外基质。通过调节微环境刚度、降解性和生化组成，我们已经确定了生物物理效应物在促进iPSC生成中的先前未知的作用。我们发现，由3D微环境施加的物理细胞限制通过加速间充质到上皮的转变和增加的表观遗传重塑来促进重编程。我们的结论是，三维微环境信号协同作用与重编程转录因子，以增加体细胞可塑性。
Since the discovery of induced pluripotent stem cells (iPSCs), numerous approaches have been explored to improve the original protocol, which is based on a two-dimensional (2D) cell-culture system. Surprisingly, nothing is known about the effect of a more biologically faithful 3D environment on somatic-cell reprogramming. Here, we report a systematic analysis of how reprogramming of somatic cells occurs within engineered 3D extracellular matrices. By modulating microenvironmental stiffness, degradability and biochemical composition, we have identified a previously unknown role for biophysical effectors in the promotion of iPSC generation. We find that the physical cell confinement imposed by the 3D microenvironment boosts reprogramming through an accelerated mesenchymal-to-epithelial transition and increased epigenetic remodelling. We conclude that 3D microenvironmental signals act synergistically with reprogramming transcription factors to increase somatic plasticity.