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Intermediate cells of in vitro cellular reprogramming and in vivo tissue regeneration require desmoplakin.

Jeongmin HaBum Suk KimByungkuk MinJuhyeon NamJae-Geun LeeMinhyung LeeByoung-Ha YoonYoon Ha ChoiIlkyun ImJung Sun ParkHyosun ChoiAreum BaekSang Mi ChoMi-Ok LeeKi-Hoan NamJi Young MunMirang KimSeon-Young KimMyung Jin SonYong-Kook KangJeong-Soo LeeJong Kyoung KimJanghwan Kim
Published in: Science advances (2022)
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 <i>Dsp</i> 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 <i>Dsp</i> 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.
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