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

Weibin Cai; Jing Tan; Jianyun Yan; Lu Zhang; Xiaoqiang Cai; Haiping Wang; Fang Liu; Maoqing Ye; Chen-Leng Cai

doi:10.1016/j.celrep.2019.06.003

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

Cell Rep. 2019 Jul 2;28(1):190-201.e3. doi: 10.1016/j.celrep.2019.06.003.

Authors

Weibin Cai¹, Jing Tan², Jianyun Yan³, Lu Zhang⁴, Xiaoqiang Cai³, Haiping Wang², Fang Liu⁵, Maoqing Ye⁶, Chen-Leng Cai⁷

Affiliations

¹ Department of Developmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Department of Biochemistry, Guangdong Engineering & Technology Research Center for Disease-Model Animals, Zhongshan Medical School, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China. Electronic address: [email protected].
² Department of Biochemistry, Guangdong Engineering & Technology Research Center for Disease-Model Animals, Zhongshan Medical School, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China.
³ Department of Developmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
⁴ Department of Developmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 West Walnut Street, Indianapolis, Indiana 46202, USA.
⁵ Cardiovascular Center, Children's Hospital of Fudan University, Shanghai 201102, China.
⁶ Shanghai Key Laboratory of Clinical Geriatric Medicine, Department of Cardiology, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China.
⁷ Department of Developmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Riley Heart Research Center, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 West Walnut Street, Indianapolis, Indiana 46202, USA. Electronic address: [email protected].

Abstract

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-MHC^CreERT2 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.

Keywords: cell lineage tracing; epicardial cells; heart regeneration; neonatal mouse.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Animals, Newborn
Cell Differentiation / genetics
Cell Differentiation / physiology
Cell Lineage
Coronary Vessels / cytology*
Coronary Vessels / metabolism
Endothelial Cells / cytology
Endothelial Cells / metabolism
Gene Knock-In Techniques
Heart / physiology*
Heart Injuries / genetics
Heart Injuries / metabolism*
Mice
Myocytes, Cardiac / cytology*
Myocytes, Cardiac / metabolism
Neovascularization, Physiologic
Pericardium / cytology*
Pericardium / metabolism
Regeneration / genetics
Regeneration / physiology*
Stem Cells / cytology*
Stem Cells / metabolism
T-Box Domain Proteins / genetics
T-Box Domain Proteins / metabolism*

Substances

T-Box Domain Proteins
Tbx18 protein, mouse

Abstract

Publication types

MeSH terms

Substances

Grants and funding