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.
[1]Icahn Sch Med Mt Sinai, Dept Dev & Regenerat Biol, Black Family Stem Cell Inst, One Gustave L Levy Pl, New York, NY 10029 USA;
[2]Sun Yat Sen Univ, Guangdong Engn & Technol Res Ctr Dis Model Anim, Zhongshan Med Sch, Dept Biochem, Guangzhou 510080, Guangdong, Peoples R China;
[3]Indiana Univ Sch Med, Riley Heart Res Ctr, Herman B Wells Ctr Pediat Res, 1044 West Walnut St, Indianapolis, IN 46202 USA;
[4]Fudan Univ, Childrens Hosp, Ctr Cardiovasc, Shanghai 201102, Peoples R China;
[5]Fudan Univ, Shanghai Key Lab Clin Geriatr Med, Dept Cardiol, Huadong Hosp, Shanghai 200040, Peoples R China
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