Transcriptional Control of Cell Lineage Development in Epicardium-Derived Cells

Overview

Journal J Dev Biol

Specialty Biology

Date 2016 Nov 15

PMID 27840808

Citations 22

Authors

Caitlin M Braitsch

Katherine E Yutzey

Affiliations

Soon will be listed here.

Abstract

Epicardial derivatives, including vascular smooth muscle cells and cardiac fibroblasts, are crucial for proper development of the coronary vasculature and cardiac fibrous matrix, both of which support myocardial integrity and function in the normal heart. Epicardial formation, epithelial-to-mesenchymal transition (EMT), and epicardium-derived cell (EPDC) differentiation are precisely regulated by complex interactions among signaling molecules and transcription factors. Here we review the roles of critical transcription factors that are required for specific aspects of epicardial development, EMT, and EPDC lineage specification in development and disease. Epicardial cells and subepicardial EPDCs express transcription factors including Wt1, Tcf21, Tbx18, and Nfatc1. As EPDCs invade the myocardium, epicardial progenitor transcription factors such as Wt1 are downregulated. EPDC differentiation into SMC and fibroblast lineages is precisely regulated by a complex network of transcription factors, including Tcf21 and Tbx18. These and other transcription factors also regulate epicardial EMT, EPDC invasion, and lineage maturation. In addition, there is increasing evidence that epicardial transcription factors are reactivated with adult cardiac ischemic injury. Determining the function of reactivated epicardial cells in myocardial infarction and fibrosis may improve our understanding of the pathogenesis of heart disease.

Citing Articles

Novel Insights into the Molecular Mechanisms Governing Embryonic Epicardium Formation.

Carmona R, Lopez-Sanchez C, Garcia-Martinez V, Garcia-Lopez V, Munoz-Chapuli R, Lozano-Velasco E J Cardiovasc Dev Dis. 2023; 10(11).

PMID: 37998498 PMC: 10672416. DOI: 10.3390/jcdd10110440.

Cardiomyocyte-fibroblast crosstalk in the postnatal heart.

Uscategui Calderon M, Gonzalez B, Yutzey K Front Cell Dev Biol. 2023; 11:1163331.

PMID: 37077417 PMC: 10106698. DOI: 10.3389/fcell.2023.1163331.

leptin b and its regeneration enhancer illustrate the regenerative features of zebrafish hearts.

Shin K, Begeman I, Cao J, Kang J Dev Dyn. 2022; 253(1):91-106.

PMID: 36495292 PMC: 10256838. DOI: 10.1002/dvdy.556.

The TFEB-TGIF1 axis regulates EMT in mouse epicardial cells.

Astanina E, Doronzo G, Cora D, Neri F, Oliviero S, Genova T Nat Commun. 2022; 13(1):5191.

PMID: 36057632 PMC: 9440911. DOI: 10.1038/s41467-022-32855-3.

Upregulation of Wilms' Tumor 1 in epicardial cells increases cardiac fibrosis in dystrophic mice.

Guo Z, Geng M, Huang Y, Han G, Jing R, Lin C Cell Death Differ. 2022; 29(10):1928-1940.

PMID: 35306537 PMC: 9525265. DOI: 10.1038/s41418-022-00979-0.

References

Lu X, Wang L, Chen S, He L, Yang X, Shi Y . Genome-wide association study in Han Chinese identifies four new susceptibility loci for coronary artery disease. Nat Genet. 2012; 44(8):890-4. PMC: 3927410. DOI: 10.1038/ng.2337. View

Barnes R, Firulli B, VanDusen N, Morikawa Y, Conway S, Cserjesi P . Hand2 loss-of-function in Hand1-expressing cells reveals distinct roles in epicardial and coronary vessel development. Circ Res. 2011; 108(8):940-9. PMC: 3086599. DOI: 10.1161/CIRCRESAHA.110.233171. View

Azambuja A, Portillo-Sanchez V, Rodrigues M, Omae S, Schechtman D, Strauss B . Retinoic acid and VEGF delay smooth muscle relative to endothelial differentiation to coordinate inner and outer coronary vessel wall morphogenesis. Circ Res. 2010; 107(2):204-16. DOI: 10.1161/CIRCRESAHA.109.214650. View

Martinez-Estrada O, Lettice L, Essafi A, Guadix J, Slight J, Velecela V . Wt1 is required for cardiovascular progenitor cell formation through transcriptional control of Snail and E-cadherin. Nat Genet. 2009; 42(1):89-93. PMC: 2799392. DOI: 10.1038/ng.494. View

Plotkin M, Mudunuri V . Pod1 induces myofibroblast differentiation in mesenchymal progenitor cells from mouse kidney. J Cell Biochem. 2007; 103(2):675-90. DOI: 10.1002/jcb.21441. View

Smart N, Riley P . The epicardium as a candidate for heart regeneration. Future Cardiol. 2011; 8(1):53-69. PMC: 3977139. DOI: 10.2217/fca.11.87. View

Wu B, Zhang Z, Lui W, Chen X, Wang Y, Chamberlain A . Endocardial cells form the coronary arteries by angiogenesis through myocardial-endocardial VEGF signaling. Cell. 2012; 151(5):1083-96. PMC: 3508471. DOI: 10.1016/j.cell.2012.10.023. View

Munoz-Chapuli R, Macias D, Gonzalez-Iriarte M, Carmona R, Atencia G, Perez-Pomares J . [The epicardium and epicardial-derived cells: multiple functions in cardiac development]. Rev Esp Cardiol. 2002; 55(10):1070-82. DOI: 10.1016/s0300-8932(02)76758-4. View

Limana F, Bertolami C, Mangoni A, Di Carlo A, Avitabile D, Mocini D . Myocardial infarction induces embryonic reprogramming of epicardial c-kit(+) cells: role of the pericardial fluid. J Mol Cell Cardiol. 2009; 48(4):609-18. DOI: 10.1016/j.yjmcc.2009.11.008. View

10.

Timmerman L, Grego-Bessa J, Raya A, Bertran E, Perez-Pomares J, Diez J . Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. Genes Dev. 2004; 18(1):99-115. PMC: 314285. DOI: 10.1101/gad.276304. View

11.

Hogan P, Chen L, Nardone J, Rao A . Transcriptional regulation by calcium, calcineurin, and NFAT. Genes Dev. 2003; 17(18):2205-32. DOI: 10.1101/gad.1102703. View

12.

Quaggin S, Vanden Heuvel G, Igarashi P . Pod-1, a mesoderm-specific basic-helix-loop-helix protein expressed in mesenchymal and glomerular epithelial cells in the developing kidney. Mech Dev. 1998; 71(1-2):37-48. DOI: 10.1016/s0925-4773(97)00201-3. View

13.

Jopling C, Sleep E, Raya M, Marti M, Raya A, Izpisua Belmonte J . Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. Nature. 2010; 464(7288):606-9. PMC: 2846535. DOI: 10.1038/nature08899. View

14.

Takayanagi H, Kim S, Koga T, Nishina H, Isshiki M, Yoshida H . Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev Cell. 2002; 3(6):889-901. DOI: 10.1016/s1534-5807(02)00369-6. View

15.

Russell J, Goetsch S, Gaiano N, Hill J, Olson E, Schneider J . A dynamic notch injury response activates epicardium and contributes to fibrosis repair. Circ Res. 2010; 108(1):51-9. PMC: 3042596. DOI: 10.1161/CIRCRESAHA.110.233262. View

16.

Lie-Venema H, Eralp I, Markwald R, van den Akker N, Wijffels M, Kolditz D . Periostin expression by epicardium-derived cells is involved in the development of the atrioventricular valves and fibrous heart skeleton. Differentiation. 2008; 76(7):809-19. DOI: 10.1111/j.1432-0436.2007.00262.x. View

17.

Mu H, Ohashi R, Lin P, Yao Q, Chen C . Cellular and molecular mechanisms of coronary vessel development. Vasc Med. 2005; 10(1):37-44. DOI: 10.1191/1358863x05vm584ra. View

18.

Kraus F, Haenig B, Kispert A . Cloning and expression analysis of the mouse T-box gene Tbx18. Mech Dev. 2000; 100(1):83-6. DOI: 10.1016/s0925-4773(00)00494-9. View

19.

Acharya A, Baek S, Banfi S, Eskiocak B, Tallquist M . Efficient inducible Cre-mediated recombination in Tcf21 cell lineages in the heart and kidney. Genesis. 2011; 49(11):870-7. PMC: 3279154. DOI: 10.1002/dvg.20750. View

20.

Kikuchi K, Poss K . Cardiac regenerative capacity and mechanisms. Annu Rev Cell Dev Biol. 2012; 28:719-41. PMC: 3586268. DOI: 10.1146/annurev-cellbio-101011-155739. View