Tbx5a lineage tracing shows cardiomyocyte plasticity during zebrafish heart regeneration.

Tbx5a lineage tracing shows cardiomyocyte plasticity during zebrafish heart regeneration.
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DOI:
10.1038/s41467-017-02650-6
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发表时间:
2018-01-30
影响因子:
16.6
通讯作者:
Mercader N
Mercader N
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Sánchez-Iranzo H;Galardi-Castilla M;Minguillón C;Sanz-Morejón A;González-Rosa JM;Felker A;Ernst A;Guzmán-Martínez G;Mosimann C;Mercader N

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在发育过程中,来自第一心野(FHF)的中胚层祖细胞形成原始心管,来自第二心野(SHF)的祖细胞加入其中。FHF和SHF祖细胞对成年斑马鱼心脏的贡献迄今尚未研究。在这里,我们发现,使用遗传tbx 5a谱系追踪工具,成年斑马鱼的心室肌主要来自tbx 5a+细胞,有一小部分来自tbx 5a − SHF祖细胞。值得注意的是,胚胎中心室tbx 5a+衍生的心肌细胞的消融通过SHF衍生的细胞的扩增来补偿。在成人中,tbx 5a的表达仅限于小梁,并从外皮质层中排除。TBX 5A-谱系追踪显示,在成体心脏再生过程中,小梁心肌细胞可以转换其命运并分化为皮质心肌。我们的结论是高度的心肌细胞命运可塑性有助于有效的再生。目前还不清楚是胚胎起源还是心肌细胞的解剖位置限制了它们对斑马鱼心脏再生的贡献。在这里,作者显示了胚胎前体在tbx 5a命运定位后的可塑性,以及小梁心肌细胞有助于重建皮质心肌。
During development, mesodermal progenitors from the first heart field (FHF) form a primitive cardiac tube, to which progenitors from the second heart field (SHF) are added. The contribution of FHF and SHF progenitors to the adult zebrafish heart has not been studied to date. Here we find, using genetic tbx5a lineage tracing tools, that the ventricular myocardium in the adult zebrafish is mainly derived from tbx5a+ cells, with a small contribution from tbx5a− SHF progenitors. Notably, ablation of ventricular tbx5a+-derived cardiomyocytes in the embryo is compensated by expansion of SHF-derived cells. In the adult, tbx5a expression is restricted to the trabeculae and excluded from the outer cortical layer. tbx5a-lineage tracing revealed that trabecular cardiomyocytes can switch their fate and differentiate into cortical myocardium during adult heart regeneration. We conclude that a high degree of cardiomyocyte cell fate plasticity contributes to efficient regeneration. It is not clear if it is the embryonic origin or anatomical location of cardiomyocytes that restrict their contribution to zebrafish heart regeneration. Here, the authors show a plasticity of embryonic precursors following tbx5a fate mapping and that trabecular cardiomyocytes help to rebuild the cortical myocardium.
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