MIT华人团队:揭示细胞体积压缩对类器官生长的影响
创作:周旸 审核:周旸 01月06日
  • 许多关键生物过程都集中于细胞内有限的空间中,多种物理信号通过诱导细胞体积压缩,来调节细胞内的分子拥挤情况;
  • 细胞内的分子拥挤状态,是介导外界物理因素对细胞功能影响的重要因素;
  • 细胞内分子的拥挤状态,使得LRP6信号体可以稳定形成,显著增强了Wnt/b-catenin信号通路的信号强度;
  • 由细胞体积压缩而增强的Wnt/b-catenin信号通路,可以驱动肠道类器官中的肠干细胞的自我更新,促进类器官生长。
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周旸
MIT华人团队近日在Cell Stem Cell发表研究,发现压缩细胞体积造成的细胞内分子拥挤状态,可以通过影响Wnt/b-catenin信号通路驱动干细胞更新、促进类器官生长。该研究成果不仅揭示了一种外界物理因素对于细胞功能的影响方式,更为促进干细胞、类器官生长提供了方法,值得参考。
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Cell Stem Cell [IF:20.86]

Volumetric Compression Induces Intracellular Crowding to Control Intestinal Organoid Growth via Wnt/β-Catenin Signaling

体积压缩引起细胞内拥挤通过 Wnt/β-Catenin通路控制肠道类器官生长

10.1016/j.stem.2020.09.012

2020-10-13, Article

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Enormous amounts of essential intracellular events are crowdedly packed inside picoliter-sized cellular space. However, the significance of the physical properties of cells remains underappreciated because of a lack of evidence of how they affect cellular functionalities. Here, we show that volumetric compression regulates the growth of intestinal organoids by modifying intracellular crowding and elevating Wnt/β-catenin signaling. Intracellular crowding varies upon stimulation by different types of extracellular physical/mechanical cues and leads to significant enhancement of Wnt/β-catenin signaling by stabilizing the LRP6 signalosome. By enhancing intracellular crowding using osmotic and mechanical compression, we show that expansion of intestinal organoids was facilitated through elevated Wnt/β-catenin signaling and greater intestinal stem cell (ISC) self-renewal. Our results provide an entry point for understanding how intracellular crowdedness functions as a physical regulator linking extracellular physical cues with intracellular signaling and potentially facilitate the design of engineering approaches for expansion of stem cells and organoids.

First Authors:
Yiwei Li,Maorong Chen

Correspondence Authors:
Ming Guo

All Authors:
Yiwei Li,Maorong Chen,Jiliang Hu,Ren Sheng,Qirong Lin,Xi He,Ming Guo

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