title: Mammalian heart renewal by pre-existing cardiomyocytes.
abstract: Although recent studies have revealed that heart cells are generated in adult mammals, the frequency of generation and the source of new heart cells are not yet known. Some studies suggest a high rate of stem cell activity with differentiation of progenitors to cardiomyocytes. Other studies suggest that new cardiomyocytes are born at a very low rate, and that they may be derived from the division of pre-existing cardiomyocytes. Here we show, by combining two different pulse-chase approaches--genetic fate-mapping with stable isotope labelling, and multi-isotope imaging mass spectrometry--that the genesis of cardiomyocytes occurs at a low rate by the division of pre-existing cardiomyocytes during normal ageing, a process that increases adjacent to areas of myocardial injury. We found that cell cycle activity during normal ageing and after injury led to polyploidy and multinucleation, but also to new diploid, mononucleate cardiomyocytes. These data reveal pre-existing cardiomyocytes as the dominant source of cardiomyocyte replacement in normal mammalian myocardial homeostasis as well as after myocardial injury.
authors.affiliation: Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, Massachusetts 02139, USA.
authors.forename: Samuel E
authors.initials: SE
authors.lastname: Senyo
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Steinhauser
authors.forename: Christie L
authors.initials: CL
authors.lastname: Pizzimenti
authors.forename: Vicky K
authors.initials: VK
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Cai
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.forename: Ting-Di
authors.initials: TD
authors.lastname: Wu
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Guerquin-Kern
authors.forename: Claude P
authors.initials: CP
authors.lastname: Lechene
authors.forename: Richard T
authors.initials: RT
authors.lastname: Lee
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D002453:Cell Cycle; D004247:DNA / Q000096:biosynthesis; D005260:Female; D006321:Heart; D006706:Homeostasis; D007553:Isotope Labeling; D008297:Male; D008322:Mammals; D013058:Mass Spectrometry; D051379:Mice; D032386:Myoblasts, Cardiac / Q000166:cytology; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D011123:Polyploidy; D012038:Regeneration
chemical_list: D004247:DNA