小柯机器人

美国哈佛大学Sharad Ramanathan等研究人员合作发现，控制类器官对称性的破坏揭示出人类轴向延伸背后的一个兴奋系统。2023年1月18日，国际知名学术期刊《细胞》在线发表了这一成果。

研究人员开发了一个生物工程和机器学习框架，通过调整它们的空间耦合来优化类器官的对称性破坏。这个框架使得可重复地生成轴向伸长的类器官，每个类器官拥有一个尾芽和神经管。研究人员发现，一个由WNT/FGF信号组成的兴奋系统通过诱导一个类似神经外胚层的信号中心来驱动延伸。研究人员发现，兴奋系统的不稳定性被分泌的WNT抑制剂所抑制。缺少这些抑制剂会导致异位的尾芽和分支。这些结果确定了管理人类稳定轴向延伸的机制。

研究人员表示，人类胚胎打破对称性，形成身体的前后轴。当胚胎沿着这条轴线延伸时，尾芽中的祖先产生了产生脊髓、骨骼和肌肉的组织。这就提出了一个问题：胚胎是如何实现轴向延伸和模式化的。虽然体外研究有伦理上的优势，但类器官系统的变异性阻碍了机理上的洞察力。

附：英文原文

Title: Controlling organoid symmetry breaking uncovers an excitable system underlying human axial elongation

Author: Giridhar M. Anand, Heitor C. Megale, Sean H. Murphy, Theresa Weis, Zuwan Lin, Yichun He, Xiao Wang, Jia Liu, Sharad Ramanathan

Issue&Volume: 2023-01-18

Abstract: The human embryo breaks symmetry to form the anterior-posterior axis of the body.As the embryo elongates along this axis, progenitors in the tail bud give rise totissues that generate spinal cord, skeleton, and musculature. This raises the questionof how the embryo achieves axial elongation and patterning. While ethics necessitatein vitro studies, the variability of organoid systems has hindered mechanistic insights. Here,we developed a bioengineering and machine learning framework that optimizes organoidsymmetry breaking by tuning their spatial coupling. This framework enabled reproduciblegeneration of axially elongating organoids, each possessing a tail bud and neuraltube. We discovered that an excitable system composed of WNT/FGF signaling driveselongation by inducing a neuromesodermal progenitor-like signaling center. We discoveredthat instabilities in the excitable system are suppressed by secreted WNT inhibitors.Absence of these inhibitors led to ectopic tail buds and branches. Our results identifymechanisms governing stable human axial elongation.

DOI: 10.1016/j.cell.2022.12.043

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)01586-0