Limited Regeneration Potential with Minimal Epicardial Progenitor Conversions in the Neonatal Mouse Heart after Injury

Limited Regeneration Potential with Minimal Epicardial Progenitor Conversions in the Neonatal Mouse Heart after Injury
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受伤后新生小鼠心脏再生潜力有限,心外膜祖细胞转化最小

DOI:
10.1016/j.celrep.2019.06.003
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发表时间:
2019-07-02
期刊:
影响因子:
8.8
通讯作者:
Cai, Chen-Leng
Cai, Chen-Leng
中科院分区:
生物学1区
文献类型:
--
作者:
Cai, Weibin;Tan, Jing;Cai, Chen-Leng

文献摘要

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新生小鼠心脏的再生能力是有争议的。此外,心外膜细胞是否提供了一个祖细胞库从头心脏再生不完全确定。新生小鼠心脏心尖切除后,我们观察到有限的再生潜力。Tbx 18(MerCreMer)小鼠的命运图显示,新形成的冠状血管和有限数量的心肌细胞来自T-box转录因子18(Tbx 18)谱系。然而,对SM-MHCCreERT 2和Nfactc 1(Cre)小鼠的进一步谱系追踪显示,新的平滑肌和内皮细胞实际上是预先存在的冠状动脉血管的衍生物。我们的数据表明,新生小鼠心脏可以再生,但其潜力是有限的。此外,尽管心外膜细胞在胚胎发生期间是多能的,但它们通过“干”或“祖”细胞转化对心脏修复的贡献在出生后是最小的。这些观察结果表明,早期胚胎心脏发育和出生后心脏再生是不同的生物学过程。出生后心外膜细胞的多能性显著降低。
The regeneration capacity of neonatal mouse heart is controversial. In addition, whether epicardial cells provide a progenitor pool for de novo heart regeneration is incompletely defined. Following apical resection of the neonatal mouse heart, we observed limited regeneration potential. Fate-mapping of Tbx18(MerCreMer) mice revealed that newly formed coronary vessels and a limited number of cardiomyocytes were derived from the T-box transcription factor 18 (Tbx18) lineage. However, further lineage tracing with SM-MHCCreERT2 and Nfactc1(Cre) mice revealed that the new smooth muscle and endothelial cells are in fact derivatives of pre-existing coronary vessels. Our data show that neonatal mouse heart can regenerate but that its potential is limited. Moreover, although epicardial cells are multipotent during embryogenesis, their contribution to heart repair through "stem" or "progenitor" cell conversion is minimal after birth. These observations suggest that early embryonic heart development and postnatal heart regeneration are distinct biological processes. Multipotency of epicardial cells is significantly decreased after birth.