Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation.
Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation.
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作者：
虽然哺乳动物的心脏几乎没有再生能力，但人们越来越主动地确定是否可以诱导现有的心肌细胞或祖细胞引发再生反应。与哺乳动物相比，许多非哺乳类脊椎动物物种能够再生心脏，包括斑马鱼，它可以在切断高达20%的心室后完全再生心脏。为了直接解决斑马鱼心脏再生过程中新形成的心肌细胞的来源，我们首先建立了一个遗传策略，以谱系追踪心肌细胞在成鱼，基于Cre/lox系统广泛用于小鼠。使用这个系统，我们在这里显示，再生的心肌细胞来自分化的心肌细胞的增殖。此外，我们发现，增殖心肌细胞经历有限的去分化，其特征在于其肌节结构的解体，彼此分离和细胞周期进程的调节因子的表达。具体来说，我们表明，polo样激酶1（plk 1）是心脏再生过程中心肌细胞增殖的重要组成部分。我们的数据提供了第一个直接证据的来源增殖心肌细胞在斑马鱼心脏再生，并表明干/祖细胞并没有显着参与这一过程。
Although mammalian hearts show virtually no ability to regenerate, there is a growing initiative to determine whether existing cardiomyocytes or progenitor cells can be coaxed into eliciting a regenerative response. In contrast to mammals, a number of non-mammalian vertebrate species are able to regenerate their hearts, including the zebrafish, which can fully regenerate its heart following amputation of up to 20% of the ventricle. To directly address the source of newly formed cardiomyocytes during zebrafish heart regeneration, we first established a genetic strategy to lineage-trace cardiomyocytes in the adult fish, based on the Cre/lox system widely used in the mouse. Using this system, we show here that regenerated heart muscle cells are derived from the proliferation of differentiated cardiomyocytes. Furthermore, we show that proliferating cardiomyocytes undergo limited dedifferentiation characterized by the disassembly of their sarcomeric structure, detachment from one another and expression of regulators of cell cycle progression. Specifically, we show that polo-like kinase1 (plk1) is an essential component of cardiomyocyte proliferation during heart regeneration. Our data provides the first direct evidence for the source of proliferating cardiomyocytes during zebrafish heart regeneration and indicates that stem/progenitor cells are not significantly involved in this process.
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影响因子：
3
作者：
Sleep, Eduard;Boue, Stephanie;Izpisua Belmonte, Juan Carlos
通讯作者：
Izpisua Belmonte, Juan Carlos
影响因子：
56.9
作者：
Poss, KD;Wilson, LG;Keating, MT
通讯作者：
Keating, MT
影响因子：
64.5
作者：
Bersell, Kevin;Arab, Shima;Kuehn, Bernhard
通讯作者：
Kuehn, Bernhard
DOI：
10.1073/pnas.1834204100
发表时间：
2003-09-30
影响因子：
11.1
作者：
Raya, A;Koth, CM;Izpisúa-Belmonte, JC
通讯作者：
Izpisúa-Belmonte, JC
影响因子：
64.8
作者：
Dor, Y;Brown, J;Melton, DA
通讯作者：
Melton, DA