德国明斯特大学Wegner Seraphine V.团队报道了多能合成细胞中适应性金属离子转运和金属调控驱动的分化。相关研究成果发表在2024年12月23日出版的《自然—化学》。

多能细胞可以产生不同的细胞类型，这取决于它们在细胞激活或去激活功能并保留先前输入记忆时，遇到的特定分化信号序列。

该文中，研究人员通过掺入三种休眠的载脂蛋白金属酶，在合成细胞中实现了多能性，使它们能够根据特定金属离子与离子载体的运输顺序，分化为不同的功能。在第一个分化步骤中，研究人员选择性地将三种细胞外金属离子辅因子之一，转运到多能巨型单层囊泡（GUV）中，导致细胞内pH值升高、过氧化氢产生或GUV裂解。

原子模拟证实，由于膜中离子载体之间的相互作用，先前添加的离子载体抑制了后续离子载体的运输。因此，添加第二种离子载体会在多能性GUV中引发抑制反应，而添加第三种离子载体则不会导致进一步的反应，这让人想起终末分化的GUV。根据添加三种离子载体的顺序，多能GUV可以分化为五种最终功能。

附：英文原文

Title: Adaptive metal ion transport and metalloregulation-driven differentiation in pluripotent synthetic cells

Author: Higashi, Sayuri L., Zheng, Yanjun, Chakraborty, Taniya, Alavizargar, Azadeh, Heuer, Andreas, Wegner, Seraphine V.

Issue&Volume: 2024-12-23

Abstract: Pluripotent cells can yield different cell types determined by the specific sequence of differentiation signals that they encounter as the cell activates or deactivates functions and retains memory of previous inputs. Here, we achieved pluripotency in synthetic cells by incorporating three dormant apo-metalloenzymes such that they could differentiate towards distinct fates, depending on the sequence of specific metal ion transport with ionophores. In the first differentiation step, we selectively transported one of three extracellular metal ion cofactors into pluripotent giant unilamellar vesicles (GUVs), which resulted in elevation of intracellular pH, hydrogen peroxide production or GUV lysis. Previously added ionophores suppress transport with subsequent ionophores owing to interactions among them in the membrane, as corroborated by atomistic simulations. Consequently, the addition of a second ionophore elicits a dampened response in the multipotent GUV and a third ionophore results in no further response, reminiscent of a terminally differentiated GUV. The pluripotent GUV can differentiate into five final fates, depending on the sequence in which the three ionophores are added.

DOI: 10.1038/s41557-024-01682-y

Source: https://www.nature.com/articles/s41557-024-01682-y