美国加州大学旧金山分校Wendell A. Lim和Satoshi Toda研究组合作取得进展。他们建立了可以对多细胞模式进行编程的工程合成形态发生系统。该研究于2020年10月16日发表于《科学》杂志。

为了探究什么功能足以进行位置编码，他们问是否可以将任意分子（例如绿色荧光蛋白或mCherry）转化为合成形态发生子。从局部来源表达的合成形态发生子在被表面锚定蛋白捕获时会形成一个梯度，并且可以被合成受体感知。

尽管它们很简单，但这些形态发生系统产生的模式让人想起体内观察到的模式。可以通过更改锚点密度或通过提供竞争性抑制剂来重塑梯度。 可以通过向接收细胞响应回路添加反馈环或形态发生素级联来更改梯度解释。正交细胞间通信系统提供了对形态发生子进化见解以及用于组织工程的平台。

据了解，在后生动物组织中，细胞通过感知由专门的形态发生蛋白提供的位置信息来决定命运。

附：英文原文

Title: Engineering synthetic morphogen systems that can program multicellular patterning

Author: Satoshi Toda, Wesley L. McKeithan, Teemu J. Hakkinen, Pilar Lopez, Ophir D. Klein, Wendell A. Lim

Issue&Volume: 2020/10/16

Abstract: In metazoan tissues, cells decide their fates by sensing positional information provided by specialized morphogen proteins. To explore what features are sufficient for positional encoding, we asked whether arbitrary molecules (e.g., green fluorescent protein or mCherry) could be converted into synthetic morphogens. Synthetic morphogens expressed from a localized source formed a gradient when trapped by surface-anchoring proteins, and they could be sensed by synthetic receptors. Despite their simplicity, these morphogen systems yielded patterns reminiscent of those observed in vivo. Gradients could be reshaped by altering anchor density or by providing a source of competing inhibitor. Gradient interpretation could be altered by adding feedback loops or morphogen cascades to receiver cell response circuits. Orthogonal cell-cell communication systems provide insight into morphogen evolution and a platform for engineering tissues.

DOI: 10.1126/science.abc0033

Source: https://science.sciencemag.org/content/370/6514/327