Spatial Stem Cell Fate Engineering via Facile Morphogen Localization.
Spatial Stem Cell Fate Engineering via Facile Morphogen Localization.
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DOI：
10.1002/adhm.202100995
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发表时间：
2021-11
影响因子：
10
通讯作者：
Palecek SP
中科院分区：
文献类型：
--
作者：
Jin G;Floy ME;Simmons AD;Arthur MM;Palecek SP
时空控制的介绍形态和精心调制的信号通路引起模式的形成过程中的发展。虽然这一过程对于正确的器官发生至关重要，但人类发育生物学的机制受到与研究人类胚胎相关的实践和伦理挑战的限制。人类多能干细胞（hPSC）已被用于体外模拟人类发育，然而，精确时空控制细胞微环境的困难限制了该模型在探索模式形成机制中的效用。在这里，我们提出了一种简单而通用的方法，通过在基质上局部吸附形态发生剂，在2D中对hPSC分化进行空间模式化。包括BMP 4、头蛋白、激活素A和Wnt3a的形态发生素被图案化以诱导来自hPSC和hPSC衍生的祖细胞的局部中内胚层、内胚层、心肌细胞（CM）和心外膜细胞（EpiC）分化。模式化的CM和EpiC共分化允许以空间控制的方式研究这些细胞之间的相互作用，并证明了接近分化的EpiC的CM（成熟度和协调功能的重要度量）的改进的对齐。这种简单的方法提供了一个平台，在早期发展的时空模式形成的控制，系统的研究。此外，这项研究提供了一种简便的方法来生成2D图案化的hPSC衍生的组织结构，用于建模疾病和药物相互作用。本研究提出了一种简单而通用的方法来产生模式化的干细胞分化。通过限制蛋白质溶液来实现形态发生剂在基底上的沉积，并且其衍生出允许在空间背景下研究细胞相互作用的干细胞的局部分化。
Spatiotemporally controlled presentation of morphogens and elaborate modulation of signaling pathways elicit pattern formation during development. Though this process is critical for proper organogenesis, unraveling mechanisms of human developmental biology have been restricted by practical and ethical challenges associated with studying human embryos. Human pluripotent stem cells (hPSCs) have been used to model human development in vitro, however difficulties in precise spatiotemporal control of the cell microenvironment have limited the utility of this model in exploring mechanisms of pattern formation. Here, we present a simple and versatile method to spatially pattern hPSC differentiation in 2D via localized adsorption of morphogens on substrates. Morphogens including BMP4, noggin, activin A, and Wnt3a are patterned to induce localized mesendoderm, endoderm, cardiomyocyte (CM), and epicardial cell (EpiC) differentiation from hPSCs and hPSC-derived progenitors. Patterned CM and EpiC co-differentiation allows investigation of interactions between these cells in a spatially controlled manner and demonstrated improved alignment of CMs, an important metric of maturity and coordinated function, in proximity to differentiating EpiCs. This simple approach provides a platform for the controlled, systematic study of spatiotemporal pattern formation during early development. Moreover, this study provides a facile approach to generate 2D patterned hPSC-derived tissue structures for modeling disease and drug interactions. A simple and versatile approach to generate patterned stem cell differentiation is suggested in this study. Deposition of morphogens on substrate is achieved by confining protein solution and it derives localized differentiation of stem cells which allows investigation of cellular interaction in a spatial context.
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影响因子：
4.8
作者：
Kadari, Asifiqbal;Mekala, SubbaRao;Wagner, Nicole;Malan, Daniela;Koeth, Jessica;Doll, Katharina;Stappert, Laura;Eckert, Daniela;Peitz, Michael;Matthes, Jan;Sasse, Philipp;Herzig, Stefan;Bruestle, Oliver;Erguen, Suleyman;Edenhofer, Frank
通讯作者：
Edenhofer, Frank
影响因子：
15.3
作者：
Haynes, B F;Scearce, R M;Lobach, D F;Hensley, L L
通讯作者：
Hensley, L L
影响因子：
--
作者：
Giacomelli, Elisa;Bellin, Milena;Mummery, Christine L
通讯作者：
Mummery, Christine L
影响因子：
4.6
作者：
Britton, George;Heemskerk, Idse;Warmflash, Aryeh
通讯作者：
Warmflash, Aryeh
影响因子：
21.3
作者：
通讯作者：
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