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Cells
Volume 14
Issue 22
10.3390/cells14221751
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Epicardial Abnormalities and Mesenchymal/Hematopoietic Cell Expansion in Plakophilin 2-Null Mouse Embryonic Hearts

by
Mistura Dolapo Bolaji
1,
Pia E. Hartmann
2,
Eva Miriam Buhl
3,
Robin M. W. Colpaert
2,
Francesca Gasparella
4,
Leon J. de Windt
2,
Martina Calore
2,4,
Rudolf E. Leube
1 and
Hoda Moazzen
1,*
1
Institute of Molecular and Cellular Anatomy, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany
2
School of Cardiovascular Disease (CARIM), Faculty of Health, Medicine & Life Sciences (FHML), Maastricht University, Universiteitssingel 50, 6229ER Maastricht, The Netherlands
3
Electron Microscopy Facility, Institute of Pathology, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074 Aachen, Germany
4
Department of Biology, Padova University, via Ugo Bassi 58B, 35131 Padova, Italy
*
Author to whom correspondence should be addressed.
Cells 2025, 14(22), 1751; https://doi.org/10.3390/cells14221751 (registering DOI)
Submission received: 9 May 2025 / Revised: 27 October 2025 / Accepted: 4 November 2025 / Published: 8 November 2025
(This article belongs to the Special Issue The Cell Biology of Heart Disease)
Versions Notes

Abstract

Desmosomal junctions provide structural stability supporting concerted cardiomyocyte contractility. Previously, we demonstrated that a deficiency in the desmosomal transmembrane cadherin desmoglein 2 (Dsg2) reduces desmosome formation and disrupts cardiac morphogenesis, leading to excessive endothelial-to-hematopoietic cell transformation and embryonic lethality. It remained unclear whether this phenotype was specifically driven by Dsg2-deficiency or was a broader consequence of impaired desmosome adhesion. To address this question, we generated Pkp2mt/mt mouse embryos lacking the desmosomal plaque protein Pkp2, which resulted in loss of desmosome formation. Despite the absence of cardiac wall rupture, Pkp2mt/mt and some Pkp2wt/mt presented accumulations of Ter-119+ blood cells and RUNX1+/CD44+ hematopoietic stem cells in the pericardial space. Remarkably, in Pkp2mt/mt hearts, the epicardium was detached from the myocardium, contained rounded cells expressing the hematopoietic stem cell marker RUNX1, and showed altered intermediate filament expression. These findings suggest a potential trans-differentiation of the epicardial cells into hematopoietic cells. In conclusion, deficiencies in both Dsg2 and Pkp2 promote hematopoiesis in the developing murine heart but target different cell types, i.e., endothelial cells, which lack desmosomes, or desmosome-containing epicardial cells. Our results provide evidence for the involvement of Pkp2 in epicardial morphogenesis and remodeling.
Keywords: desmosome; plakophilin 2; hematopoiesis; hemopericardium; embryonic heart; heart development; intercellular junctions desmosome; plakophilin 2; hematopoiesis; hemopericardium; embryonic heart; heart development; intercellular junctions

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MDPI and ACS Style

Bolaji, M.D.; Hartmann, P.E.; Buhl, E.M.; Colpaert, R.M.W.; Gasparella, F.; Windt, L.J.d.; Calore, M.; Leube, R.E.; Moazzen, H. Epicardial Abnormalities and Mesenchymal/Hematopoietic Cell Expansion in Plakophilin 2-Null Mouse Embryonic Hearts. Cells 2025, 14, 1751. https://doi.org/10.3390/cells14221751

AMA Style

Bolaji MD, Hartmann PE, Buhl EM, Colpaert RMW, Gasparella F, Windt LJd, Calore M, Leube RE, Moazzen H. Epicardial Abnormalities and Mesenchymal/Hematopoietic Cell Expansion in Plakophilin 2-Null Mouse Embryonic Hearts. Cells. 2025; 14(22):1751. https://doi.org/10.3390/cells14221751

Chicago/Turabian Style

Bolaji, Mistura Dolapo, Pia E. Hartmann, Eva Miriam Buhl, Robin M. W. Colpaert, Francesca Gasparella, Leon J. de Windt, Martina Calore, Rudolf E. Leube, and Hoda Moazzen. 2025. "Epicardial Abnormalities and Mesenchymal/Hematopoietic Cell Expansion in Plakophilin 2-Null Mouse Embryonic Hearts" Cells 14, no. 22: 1751. https://doi.org/10.3390/cells14221751

APA Style

Bolaji, M. D., Hartmann, P. E., Buhl, E. M., Colpaert, R. M. W., Gasparella, F., Windt, L. J. d., Calore, M., Leube, R. E., & Moazzen, H. (2025). Epicardial Abnormalities and Mesenchymal/Hematopoietic Cell Expansion in Plakophilin 2-Null Mouse Embryonic Hearts. Cells, 14(22), 1751. https://doi.org/10.3390/cells14221751

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