Incompatibility in cell adhesion constitutes a barrier to interspecies chimerism,Cell Stem Cell

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Incompatibility in cell adhesion constitutes a barrier to interspecies chimerism
Cell Stem Cell ( IF 19.8 ) Pub Date : 2024-08-23 , DOI: 10.1016/j.stem.2024.07.010
Emily Ballard ₁ , Masahiro Sakurai ₁ , Leqian Yu ₁ , Lizhong Liu ₁ , Seiya Oura ₁ , Jia Huang ₁ , Jun Wu ₂

Affiliation

Interspecies blastocyst complementation holds great potential to address the global shortage of transplantable organs by growing human organs in animals. However, a major challenge in this approach is the limited chimerism of human cells in evolutionarily distant animal hosts due to various xenogeneic barriers. Here, we reveal that human pluripotent stem cells (PSCs) struggle to adhere to animal PSCs. To overcome this barrier, we developed a synthetic biology strategy that leverages nanobody-antigen interactions to enhance interspecies cell adhesion. We engineered cells to express nanobodies and their corresponding antigens on their outer membranes, significantly improving adhesion between different species’ PSCs during in vitro assays and increasing the chimerism of human PSCs in mouse embryos. Studying and manipulating interspecies pluripotent cell adhesion will provide valuable insights into cell interaction dynamics during chimera formation and early embryogenesis.

中文翻译：

细胞粘附的不相容性构成了种间嵌合的障碍

种间囊胚互补通过在动物体内培育人体器官，具有解决全球可移植器官短缺问题的巨大潜力。然而，这种方法的一个主要挑战是，由于各种异种障碍，人类细胞在进化距离较远的动物宿主中的嵌合性有限。在这里，我们揭示了人类多能干细胞 (PSC) 难以粘附到动物 PSC 上。为了克服这一障碍，我们开发了一种合成生物学策略，利用纳米抗体-抗原相互作用来增强种间细胞粘附。我们对细胞进行了改造，使其在其外膜上表达纳米抗体及其相应的抗原，从而在体外试验中显着提高了不同物种 PSC 之间的粘附性，并增加了小鼠胚胎中人类 PSC 的嵌合性。研究和操纵种间多能细胞粘附将为嵌合体形成和早期胚胎发生过程中细胞相互作用动力学提供有价值的见解。

更新日期：2024-08-23

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