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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Geometric cues for directing the differentiation of mesenchymal stem cells
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Geometric cues for directing the differentiation of mesenchymal stem cells

机译：指导骨髓间充质干细胞分化的几何线索

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摘要

Significant efforts have been directed to understanding the factors that influence the lineage commitment of stem cells. This paper demonstrates that cell shape, independent of soluble factors, has a strong influence on the differentiation of human mesenchymal stem cells (MSCs) from bone marrow. When exposed to competing soluble differentiation signals, cells cultured in rectangles with increasing aspect ratio and in shapes with pentagonal symmetry but with different subcellular curvature-and with each occupying the same area-display different adipogenesis and osteogenesis profiles. The results reveal that geometric features that increase acto-myosin contractility promote osteogenesis and are consistent with in vivo characteristics of the microenvironment of the differentiated cells. Cytoskeletal-disrupting pharmacological agents modulate shape-based trends in lineage commitment verifying the critical role of focal adhesion and myosin-generated contractility during differentiation. Microarray analysis and pathway inhibition studies suggest that contractile cells promote osteogenesis by enhancing c-Jun N-terminal kinase (JNK) and extracellular related ki-nase (ERK1/2) activation in conjunction with elevated wingless-type (Wnt) signaling. Taken together, this work points to the role that geometric shape cues can play in orchestrating the mechano-chemical signals and paracrine/autocrine factors that can direct MSCs to appropriate fates.
机译：已经作出了巨大的努力来理解影响干细胞谱系定型的因素。本文证明，细胞形状不受可溶性因子的影响，对人骨髓间充质干细胞（MSCs）的分化有很大影响。当暴露于竞争性可溶性分化信号时，细胞以长宽比增加的矩形培养，具有五边形对称但具有不同亚细胞曲率的形状，并且每个都占据相同的面积，显示出不同的脂肪形成和成骨特性。结果表明增加肌动蛋白-肌球蛋白收缩力的几何特征促进成骨，并且与分化细胞的微环境的体内特征一致。干扰细胞骨架的药理物质可调节谱系定型中基于形状的趋势，从而验证了粘着斑和肌球蛋白在分化过程中产生的收缩性的关键作用。芯片分析和通路抑制研究表明，收缩细胞通过增强c-Jun N末端激酶（JNK）和细胞外相关激酶（ERK1 / 2）激活，同时增强无翅型（Wnt）信号传导，从而促进成骨作用。综上所述，这项工作指出了几何形状线索可以在协调机械化学信号和旁分泌/自分泌因素中发挥作用，这些信号可以指导MSC进行适当的命运。

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  • 作者

    Kristopher A. Kilian; Branimir Bugarija; Bruce T. Lahn; Milan Mrksich;

  • 作者单位

    Department of Chemistry, The University of Chicago, Chicago, IL 60637 Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637;

    rnDepartment of Human Genetics, The University of Chicago, Chicago, IL 60637 Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637;

    rnDepartment of Human Genetics, The University of Chicago, Chicago, IL 60637 Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637;

    rnDepartment of Chemistry, The University of Chicago, Chicago, IL 60637 Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    cytoskeleton; microcontact printing; wnt signaling; microenvironment;

    机译：细胞骨架微接触印刷wnt信令;微环境;

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