Stem Cell Convergence Research Center, Korea Research Institute Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon 34113, Republic of Korea.
Sci Adv. 2022 Oct 28;8(43):eabk1239. doi: 10.1126/sciadv.abk1239.
Amphibians and fish show considerable regeneration potential via dedifferentiation of somatic cells into blastemal cells. In terms of dedifferentiation, in vitro cellular reprogramming has been proposed to share common processes with in vivo tissue regeneration, although the details are elusive. Here, we identified the cytoskeletal linker protein desmoplakin (Dsp) as a common factor mediating both reprogramming and regeneration. Our analysis revealed that Dsp expression is elevated in distinct intermediate cells during in vitro reprogramming. Knockdown of impedes in vitro reprogramming into induced pluripotent stem cells and induced neural stem/progenitor cells as well as in vivo regeneration of zebrafish fins. Notably, reduced expression impairs formation of the intermediate cells during cellular reprogramming and tissue regeneration. These findings suggest that there is a Dsp-mediated evolutionary link between cellular reprogramming in mammals and tissue regeneration in lower vertebrates and that the intermediate cells may provide alternative approaches for mammalian regenerative therapy.
两栖动物和鱼类通过体细胞去分化为成芽细胞表现出相当大的再生潜力。就去分化而言，体外细胞重编程被提出与体内组织再生共享共同的过程，尽管细节尚不清楚。在这里，我们确定细胞骨架连接蛋白桥粒斑蛋白 (Dsp) 作为一种共同的因子，介导重编程和再生。我们的分析表明，在体外重编程过程中，Dsp 的表达在不同的中间细胞中升高。抑制 会阻碍体外重编程为诱导多能干细胞和诱导神经干细胞/祖细胞，以及斑马鱼鳍的体内再生。值得注意的是，减少 的表达会损害细胞重编程和组织再生过程中成芽细胞的形成。这些发现表明，哺乳动物的细胞重编程和较低等脊椎动物的组织再生之间存在 Dsp 介导的进化联系，并且中间细胞可能为哺乳动物的再生治疗提供替代方法。
