Actuation enhances patterning in human neural tube organoids.
Actuation enhances patterning in human neural tube organoids.
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DOI：
10.1038/s41467-021-22952-0
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发表时间：
2021-05-27
影响因子：
16.6
通讯作者：
Ranga A
中科院分区：
文献类型：
--
作者：
Abdel Fattah AR;Daza B;Rustandi G;Berrocal-Rubio MÁ;Gorissen B;Poovathingal S;Davie K;Barrasa-Fano J;Cóndor M;Cao X;Rosenzweig DH;Lei Y;Finnell R;Verfaillie C;Sampaolesi M;Dedecker P;Van Oosterwyck H;Aerts S;Ranga A
组织通过基因调控网络、细胞间通讯和机械力介导的物理相互作用实现其复杂的空间组织。目前产生体外组织的策略在很大程度上未能实现这种主动的、动态协调的机械操作，而是依赖于响应而不是施加机械力的细胞外基质。在这里，我们开发了能够驱动类器官的设备。我们表明，积极的机械力增加生长，并导致增强图案化的类器官模型的神经管来源于单一的人类多能干细胞（hPSC）。使用单细胞转录组学和免疫组织化学的组合，我们证明了由于驱动的类器官机械调节在时间限制的能力窗口中操作，并且类器官对拉伸的反应在细胞外由基质刚度和细胞内由细胞骨架收缩性和平面细胞极性介导。使用本文开发的方法消除类器官上的主动机械力是广泛适用的，并且应该能够生成更具可重现性，可编程的类器官形状，身份和模式，为在再生医学和疾病建模应用中使用这些工具开辟途径。机械力，沿着基因调控网络和细胞间信号传导，在组织的复杂组织中起着重要作用。在这里，作者描述了主动向发育中的神经管施加机械力的装置，表明机械力可以促进生长并增强图案化。
Tissues achieve their complex spatial organization through an interplay between gene regulatory networks, cell-cell communication, and physical interactions mediated by mechanical forces. Current strategies to generate in-vitro tissues have largely failed to implement such active, dynamically coordinated mechanical manipulations, relying instead on extracellular matrices which respond to, rather than impose mechanical forces. Here, we develop devices that enable the actuation of organoids. We show that active mechanical forces increase growth and lead to enhanced patterning in an organoid model of the neural tube derived from single human pluripotent stem cells (hPSC). Using a combination of single-cell transcriptomics and immunohistochemistry, we demonstrate that organoid mechanoregulation due to actuation operates in a temporally restricted competence window, and that organoid response to stretch is mediated extracellularly by matrix stiffness and intracellularly by cytoskeleton contractility and planar cell polarity. Exerting active mechanical forces on organoids using the approaches developed here is widely applicable and should enable the generation of more reproducible, programmable organoid shape, identity and patterns, opening avenues for the use of these tools in regenerative medicine and disease modelling applications. Mechanical forces, along with gene regulatory networks and cell-cell signalling, play an important role in the complex organization of tissues. Here the authors describe devices that actively apply mechanical force to developing neural tube, demonstrating that mechanical forces increase growth and enhance patterning.
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DOI：
10.1242/dev.164368
发表时间：
2018-06-26
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Ebisuya M;Briscoe J
通讯作者：
Briscoe J
影响因子：
4.6
作者：
Delile, Julien;Rayon, Teresa;Sagner, Andreas
通讯作者：
Sagner, Andreas
DOI：
10.1126/science.aav9750
发表时间：
2019-05-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Grigoryan B;Paulsen SJ;Corbett DC;Sazer DW;Fortin CL;Zaita AJ;Greenfield PT;Calafat NJ;Gounley JP;Ta AH;Johansson F;Randles A;Rosenkrantz JE;Louis-Rosenberg JD;Galie PA;Stevens KR;Miller JS
通讯作者：
Miller JS
影响因子：
7.2
作者：
LeGoff, Loic;Lecuit, Thomas
通讯作者：
Lecuit, Thomas
DOI：
10.1242/dev.126847
发表时间：
2016-06-01
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Demers CJ;Soundararajan P;Chennampally P;Cox GA;Briscoe J;Collins SD;Smith RL
通讯作者：
Smith RL