Cardiac regeneration is an ancestral trait in vertebrates that is lost both as more recent vertebrate lineages evolved to adapt to new environments and selective pressures,and as members of certain species development...Cardiac regeneration is an ancestral trait in vertebrates that is lost both as more recent vertebrate lineages evolved to adapt to new environments and selective pressures,and as members of certain species developmentally progress towards their adult forms.While higher vertebrates like humans and rodents resolve cardiac injury with permanent fibrosis and loss of cardiac output as adults,neonates of these same species can fully regenerate heart structure and function after injury–as can adult lower vertebrates like many teleost fish and urodele amphibians.Recent research has elucidated several broad factors hypothesized to contribute to this loss of cardiac regenerative potential both evolutionarily and developmentally:an oxygen-rich environment,vertebrate thermogenesis,a complex adaptive immune system,and cancer risk trade-offs.In this review,we discuss the evidence for these hypotheses as well as the cellular participators and molecular regulators by which they act to govern heart regeneration in vertebrates.展开更多
Adult mammalian cardiomyocytes are unable to proliferate to regenerate lost tissue after heart injury.Du et al.,reporting in Cell Stem Cell,employ a FUCCI-and MADM-based system to screen for small molecules combinatio...Adult mammalian cardiomyocytes are unable to proliferate to regenerate lost tissue after heart injury.Du et al.,reporting in Cell Stem Cell,employ a FUCCI-and MADM-based system to screen for small molecules combinations that produced a collaborative effect on cardiomyocyte cycling and cytokinesis.The authors generate a cocktail of five small molecules that increase cardiomyocyte proliferation and regeneration in vitro and in vivo with high efficiency,and explore its potential in cardiac regenerative repair after myocardial infarction through a new potential pathway for cardiomyocyte cell-cycle re-entry.展开更多
基金This research was made possible by NIH F31 Fellowship(S.C.),NIH(R01HL138456)Department of Defense(W81XWH1910206)Program for Breakthrough Biomedical Research,and UCSF Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research Seed Grant(G.N.H.).
文摘Cardiac regeneration is an ancestral trait in vertebrates that is lost both as more recent vertebrate lineages evolved to adapt to new environments and selective pressures,and as members of certain species developmentally progress towards their adult forms.While higher vertebrates like humans and rodents resolve cardiac injury with permanent fibrosis and loss of cardiac output as adults,neonates of these same species can fully regenerate heart structure and function after injury–as can adult lower vertebrates like many teleost fish and urodele amphibians.Recent research has elucidated several broad factors hypothesized to contribute to this loss of cardiac regenerative potential both evolutionarily and developmentally:an oxygen-rich environment,vertebrate thermogenesis,a complex adaptive immune system,and cancer risk trade-offs.In this review,we discuss the evidence for these hypotheses as well as the cellular participators and molecular regulators by which they act to govern heart regeneration in vertebrates.
基金This work is supported by NIH(R01HL138456 and R01HL157280),American Heart Association Transformation AwardTobacco-Related Disease Research Program.
文摘Adult mammalian cardiomyocytes are unable to proliferate to regenerate lost tissue after heart injury.Du et al.,reporting in Cell Stem Cell,employ a FUCCI-and MADM-based system to screen for small molecules combinations that produced a collaborative effect on cardiomyocyte cycling and cytokinesis.The authors generate a cocktail of five small molecules that increase cardiomyocyte proliferation and regeneration in vitro and in vivo with high efficiency,and explore its potential in cardiac regenerative repair after myocardial infarction through a new potential pathway for cardiomyocyte cell-cycle re-entry.
