清华教师在干细胞世系分化研究中取得重要进展

细胞海洋

清华大学航天航空学院生物力学所教师杜婧、杨春、冯西桥等人在细胞外基质弹性诱导干细胞世系分化的研究取得重要进展。相关的研究论文“Integrin activation and internalization on soft ECM as a mechanism of induction of stem cell differentiation by ECM elasticity”（整合素活化及内吞是细胞外基质弹性诱导干细胞分化的一种机制）已于近日在《美国科学院院刊》（PNAS）上发表。
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不同弹性的细胞外基质（Extracellular Matrix， ECM）可以诱导间充质干细胞分化为成神经细胞、成肌肉细胞、成骨细胞等，这一神奇的现象自2006年一经发表，就引起全球众多科学家的关注。5年来，国际生物力学界数年来一直不断探索其机理。最近这个迷人的问题有望得到解答。+ B' \5 A# R. B8 ^4 ]
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　　细胞感受ECM弹性的过程是细胞将感受到的力学刺激转化为生物化学信号的过程。该过程称为细胞力学信号转导。细胞通过黏着斑与ECM黏附。黏着斑由一系列信号分子构成，并在胞质中与细胞微丝骨架相连。这些信号分子在力学刺激作用下可产生构象变化，从而触发激酶活化、磷酸化位点暴露、信号分子胞内运输和受体配体结合强度改变等一系列分子事件。在这些信号分子中，整合素在已知的多数力学信号感知过程中都起到关键作用，是力学信号转导通路的重要起点。9 V. G4 _2 C. r/ N& x; Z. }- G% O! t
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　　清华大学航天航空学院生物力学所研究团队在论文中阐述了细胞外基质弹性诱导干细胞世系分化的研究的重要进展：较软的细胞外基质（Extracellular Matrix， ECM）易使整合素-基质蛋白复合物解离，从而触发整合素分子被细胞内吞，导致骨形态蛋白受体的亚细胞定位发生改变，使其下游信号通路被抑制，最终诱导干细胞向神经系分化。力学分析（见上图）表明：材料的弹性变化影响了整合素-基质蛋白复合物上的加载速率，因此影响了该复合物的解离力。7 i5 ~' A& v* }% ~& I9 Q/ t% D- G- F
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　　该项研究由自然科学基金和科技部“973”项目等资助。
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always_wp

力学分析也可以研究细胞生物学中的各种有趣的现象，真好

jj2570782

超级微观的力学形态也是可以被捕捉到的，生命真奇妙！

花开次第

交叉学科的潜力无限！
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飞翔的十字架

文章出来了吗 求之 我也是生物力学的 呵呵

xiaoqi

开阔了视野，科学无限！

sunsong7

重编程技术革命——niche reprogramming
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laputave

求原文。。

bid

强烈关注哦。。。。

zxmflying

Integrin activation and internalization on soft ECM as a mechanism of induction of stem cell differentiation by ECM elasticity& T1 |. W, ^3 P0 J3 g
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    Jing Dua,3 u# G" M4 ?* }4 Q; m& ~
    Xiaofei Chena,: ?: q$ h- S- S% g  ]7 v0 P
    Xudong Lianga,
  Q$ j5 X7 @. R. n4 d: \% U    Guangyao Zhanga,
" c+ R+ L4 |. x1 U/ x: U; t* a7 t    Jia Xua,
2 }$ p& p$ K& y* M  @" J& _    Linrong Hea,6 D9 F/ o9 X; O- `
    Qingyuan Zhanb,2 o+ H: g+ E' C
    Xi-Qiao Fenga,
8 U! n4 u; o0 g2 f/ G2 T    Shu Chienc,1, and
0 F3 \, s7 a# z6 l4 X* G    Chun Yanga,1
# W2 l$ v4 [1 M) LAbstract
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  J+ s. s# ?3 ?) f# z; ?The mechanism by which ECM elasticity induces lineage specification of stem cells has not been clearly understood. Integrins are well-documented mechanosensors that are positioned at the beginning of the sensing pathway. By using an antibody specifically recognizing the active conformation of β1 integrin, we observed that β1 integrin activation in bone marrow mesenchymal stem cells (BMMSCs) was induced by soft substrate to a significantly greater degree than by stiff substrate. In contrast, however, the level of cell surface integrin on soft substrate was significantly lower than that on stiff substrate. Soft substrate markedly enhanced the internalization of integrin, and this internalization was mediated mainly through caveolae/raft-dependent endocytosis. The inhibition of integrin internalization blocked the neural lineage specification of BMMSCs on soft substrate. Furthermore, soft substrate also repressed the bone morphogenetic protein (BMP)/Smad pathway at least partially through integrin-regulated BMP receptor endocytosis. A theoretical analysis based on atomic force microscopy (AFM) data indicated that integrin–ligand complexes are more easily ruptured on soft substrate; this outcome may contribute to the enhancement of integrin internalization on soft substrate. Taken together, our results suggest that ECM elasticity affects integrin activity and trafficking to modulate integrin BMP receptor internalization, thus contributing to stem cell lineage specification., l' K5 V4 M. D- q' U. n. G5 i
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