title: Turning terminally differentiated skeletal muscle cells into regenerative progenitors.
abstract: The ability to repeatedly regenerate limbs during the entire lifespan of an animal is restricted to certain salamander species among vertebrates. This ability involves dedifferentiation of post-mitotic cells into progenitors that in turn form new structures. A long-term enigma has been how injury leads to dedifferentiation. Here we show that skeletal muscle dedifferentiation during newt limb regeneration depends on a programmed cell death response by myofibres. We find that programmed cell death-induced muscle fragmentation produces a population of 'undead' intermediate cells, which have the capacity to resume proliferation and contribute to muscle regeneration. We demonstrate the derivation of proliferating progeny from differentiated, multinucleated muscle cells by first inducing and subsequently intercepting a programmed cell death response. We conclude that cell survival may be manifested by the production of a dedifferentiated cell with broader potential and that the diversion of a programmed cell death response is an instrument to achieve dedifferentiation.
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institute, Solna, Sweden.
authors.forename: Heng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institute, Solna, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Lööf
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institute, Solna, Sweden.
authors.forename: Paula
authors.initials: P
authors.lastname: Borg
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institute, 17177 Stockholm, Sweden.
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Nader
authors.affiliation: Baxter Laboratory for Stem Cell Biology, Stanford University, Stanford, California 94305, United States.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Blau
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institute, Solna, Sweden.
authors.forename: András
authors.initials: A
authors.lastname: Simon
mesh_terms: D000818:Animals; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D054337:Cell Dedifferentiation; D049109:Cell Proliferation; D005260:Female; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D018485:Muscle Fibers, Skeletal; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D009673:Notophthalmus viridescens / Q000502:physiology*; D012038:Regeneration
chemical_list: D020169:Caspases