Purkinje Cardiomyocytes of the Adult Ventricular Conduction System Are Highly Diploid but Not Uniquely Regenerative

被引:2
|
作者
Watanabe, Hirofumi [1 ]
Tao, Ge [1 ]
Gan, Peiheng [1 ]
Westbury, Baylee C. [1 ]
Cox, Kristie D. [1 ]
Tjen, Kelsey [1 ]
Song, Ruolan [1 ]
Fishman, Glenn I. [2 ]
Makita, Takako [3 ]
Sucov, Henry M. [1 ,4 ]
机构
[1] Med Univ South Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA
[2] New York Univ, Leon H Charney Div Cardiol, Grossman Sch Med, New York, NY 10016 USA
[3] Med Univ South Carolina, Darby Childrens Res Inst, Dept Pediat, Charleston, SC 29425 USA
[4] Med Univ South Carolina, Dept Med, Div Cardiol, Charleston, SC 29425 USA
基金
美国国家卫生研究院;
关键词
polyploidy; diploid cardiomyocyte; heart regeneration; conduction system; Purkinje cell; HEART REGENERATION; POLYPLOIDIZATION; BINUCLEATION; RENEWAL;
D O I
10.3390/jcdd10040161
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Adult hearts are characterized by inefficient regeneration after injury, thus, the features that support or prevent cardiomyocyte (CM) proliferation are important to clarify. Diploid CMs are a candidate cell type that may have unique proliferative and regenerative competence, but no molecular markers are yet known that selectively identify all or subpopulations of diploid CMs. Here, using the conduction system expression marker Cntn2-GFP and the conduction system lineage marker Etv1Cre(ERT2), we demonstrate that Purkinje CMs that comprise the adult ventricular conduction system are disproportionately diploid (33%, vs. 4% of bulk ventricular CMs). These, however, represent only a small proportion (3%) of the total diploid CM population. Using EdU incorporation during the first postnatal week, we demonstrate that bulk diploid CMs found in the later heart enter and complete the cell cycle during the neonatal period. In contrast, a significant fraction of conduction CMs persist as diploid cells from fetal life and avoid neonatal cell cycle activity. Despite their high degree of diploidy, the Purkinje lineage had no enhanced competence to support regeneration after adult heart infarction.
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页数:15
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