{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T19:18:33Z","timestamp":1775330313087,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T00:00:00Z","timestamp":1762560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"START Program of the Medizinische Fakult\u00e4t, RWTH Aachen University","award":["81-02.04.2020.A323"],"award-info":[{"award-number":["81-02.04.2020.A323"]}]},{"name":"Horizon-EIC-2022-Pathfinder","award":["IMPACT; 101115536"],"award-info":[{"award-number":["IMPACT; 101115536"]}]},{"name":"Fondazione Cariparo Starting Package","award":["C93C22008360007"],"award-info":[{"award-number":["C93C22008360007"]}]},{"DOI":"10.13039\/501100002426","name":"Telethon Foundation","doi-asserted-by":"crossref","award":["GMR24T1105"],"award-info":[{"award-number":["GMR24T1105"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"crossref"}]},{"name":"\u201cTopconsortia for Knowledge and Innovation\u201d (TKI) Health~Holland","award":["LSHM21068"],"award-info":[{"award-number":["LSHM21068"]}]},{"name":"\u201cTopconsortia for Knowledge and Innovation\u201d (TKI) Health~Holland","award":["LSHM202313"],"award-info":[{"award-number":["LSHM202313"]}]},{"name":"Cardinnov-RECREATE of the Dutch Research Council","award":["GA N\u00b0 101095426"],"award-info":[{"award-number":["GA N\u00b0 101095426"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cells14221751","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T10:35:31Z","timestamp":1762770931000},"page":"1751","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Epicardial Abnormalities and Mesenchymal\/Hematopoietic Cell Expansion in Plakophilin 2-Null Mouse Embryonic Hearts"],"prefix":"10.3390","volume":"14","author":[{"given":"Mistura Dolapo","family":"Bolaji","sequence":"first","affiliation":[{"name":"Institute of Molecular and Cellular Anatomy, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7452-5462","authenticated-orcid":false,"given":"Pia E.","family":"Hartmann","sequence":"additional","affiliation":[{"name":"School of Cardiovascular Disease (CARIM), Faculty of Health, Medicine & Life Sciences (FHML), Maastricht University, Universiteitssingel 50, 6229ER Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0627-9228","authenticated-orcid":false,"given":"Eva Miriam","family":"Buhl","sequence":"additional","affiliation":[{"name":"Electron Microscopy Facility, Institute of Pathology, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7689-4467","authenticated-orcid":false,"given":"Robin M. W.","family":"Colpaert","sequence":"additional","affiliation":[{"name":"School of Cardiovascular Disease (CARIM), Faculty of Health, Medicine & Life Sciences (FHML), Maastricht University, Universiteitssingel 50, 6229ER Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8731-6273","authenticated-orcid":false,"given":"Francesca","family":"Gasparella","sequence":"additional","affiliation":[{"name":"Department of Biology, Padova University, via Ugo Bassi 58B, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7793-2856","authenticated-orcid":false,"given":"Leon J. de","family":"Windt","sequence":"additional","affiliation":[{"name":"School of Cardiovascular Disease (CARIM), Faculty of Health, Medicine & Life Sciences (FHML), Maastricht University, Universiteitssingel 50, 6229ER Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4751-1476","authenticated-orcid":false,"given":"Martina","family":"Calore","sequence":"additional","affiliation":[{"name":"School of Cardiovascular Disease (CARIM), Faculty of Health, Medicine & Life Sciences (FHML), Maastricht University, Universiteitssingel 50, 6229ER Maastricht, The Netherlands"},{"name":"Department of Biology, Padova University, via Ugo Bassi 58B, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5519-7379","authenticated-orcid":false,"given":"Rudolf E.","family":"Leube","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cellular Anatomy, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8607-6545","authenticated-orcid":false,"given":"Hoda","family":"Moazzen","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cellular Anatomy, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/s41569-018-0086-9","article-title":"The deployment of cell lineages that form the mammalian heart","volume":"15","author":"Meilhac","year":"2018","journal-title":"Nat. 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