학술논문

Mammalian heart renewal by pre-existing cardiomyocytes.
Document Type
Article
Source
Nature. 1/17/2013, Vol. 493 Issue 7432, p433-436. 4p. 4 Diagrams, 2 Charts.
Subject
*MAMMALS
*HEART cells
*MASS spectrometry
*POLYPLOIDY
*PANGOLINS
*STEM cells
*SPECTRUM analysis
Language
ISSN
0028-0836
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. [ABSTRACT FROM AUTHOR]