Existing cardiomyocytes generate cardiomyocytes at a low rate after birth in mice
Existing cardiomyocytes generate cardiomyocytes at a low rate after birth in mice
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DOI：
10.1073/pnas.1408233111
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发表时间：
2014-06-17
影响因子：
11.1
通讯作者：
Ardehali, Reza
中科院分区：
文献类型：
--
作者：
Ali, Shah R.;Hippenmeyer, Simon;Ardehali, Reza
长期以来，哺乳动物的心脏一直被认为是有丝分裂后的器官，这意味着心肌细胞的总数是在出生时确定的。哺乳动物心脏细胞分裂的分析因出生后不久的心肌细胞双核而变得复杂，这使得解释传统的细胞周转测定具有挑战性[Laflamme MA， Murray CE (2011) Nature 473(7347): 326-335；王晓明，王晓明。（2009）科学进展(5):1 - 4。一种优雅的多同位素成像-质谱技术最近计算出小鼠心肌细胞生成的低离散率[Senyo SE， et al. (2013) Nature 493(7432): 433-436]，但我们对出生后心肌发生的细胞水平理解仍然有限。本研究利用“双标记镶嵌分析”小鼠模型，为分化的α -肌球蛋白重链表达心肌细胞作为出生后心肌发生的起源细胞提供了新的证据。我们发现，有限的、终生的、对称的心肌细胞分裂是一种罕见的现象，在子宫内很明显，但在小鼠出生后的第一个月显著减少；子心肌细胞很少分裂，据我们所知，这项研究首次证实了这一点。此外，结扎左冠状动脉前降支（在双标记小鼠的马赛克分析中导致心肌梗死）在损伤后4周内并没有使心肌细胞分裂率高于基础水平。这里描述的克隆分析提供了哺乳动物出生后心肌发生的直接证据。
The mammalian heart has long been considered a postmitotic organ, implying that the total number of cardiomyocytes is set at birth. Analysis of cell division in the mammalian heart is complicated by cardiomyocyte binucleation shortly after birth, which makes it challenging to interpret traditional assays of cell turnover [Laflamme MA, Murray CE (2011) Nature 473(7347): 326-335; Bergmann O, et al. (2009) Science 324(5923): 98-102]. An elegant multi-isotope imaging-mass spectrometry technique recently calculated the low, discrete rate of cardiomyocyte generation in mice [Senyo SE, et al. (2013) Nature 493(7432): 433-436], yet our cellular-level understanding of postnatal cardiomyogenesis remains limited. Herein, we provide a new line of evidence for the differentiated alpha-myosin heavy chain-expressing cardiomyocyte as the cell of origin of postnatal cardiomyogenesis using the "mosaic analysis with double markers" mouse model. We show limited, life-long, symmetric division of cardiomyocytes as a rare event that is evident in utero but significantly diminishes after the first month of life in mice; daughter cardiomyocytes divide very seldom, which this study is the first to demonstrate, to our knowledge. Furthermore, ligation of the left anterior descending coronary artery, which causes a myocardial infarction in the mosaic analysis with double-marker mice, did not increase the rate of cardiomyocyte division above the basal level for up to 4 wk after the injury. The clonal analysis described here provides direct evidence of postnatal mammalian cardiomyogenesis.