Higashi Sayuri L, Zheng Yanjun, Chakraborty Taniya, Alavizargar Azadeh, Heuer Andreas, Wegner Seraphine V
Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany.
Institute for Advanced Study, Gifu University, Gifu, Japan.
Nat Chem. 2025 Jan;17(1):54-65. doi: 10.1038/s41557-024-01682-y. Epub 2024 Dec 23.
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.
多能细胞可以产生不同的细胞类型，这取决于它们在激活或失活功能并保留对先前输入的记忆时所遇到的特定分化信号序列。在这里，我们通过整合三种休眠的脱辅基金属酶在合成细胞中实现了多能性，这样它们就可以根据与离子载体进行特定金属离子转运的序列分化为不同的命运。在第一步分化中，我们将三种细胞外金属离子辅因子之一选择性地转运到多能性巨型单层囊泡（GUV）中，这导致细胞内pH值升高、过氧化氢产生或GUV裂解。由于它们在膜中的相互作用，先前添加的离子载体会抑制随后离子载体的转运，原子模拟证实了这一点。因此，添加第二种离子载体在多能性GUV中引发的反应减弱，而添加第三种离子载体则不会导致进一步反应，这让人联想到终末分化的GUV。根据添加三种离子载体的顺序，多能性GUV可以分化为五种最终命运。
