{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:32:07Z","timestamp":1760146327496,"version":"build-2065373602"},"reference-count":29,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T00:00:00Z","timestamp":1729123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"HL127236"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Notch signaling, an important signaling pathway in cardiac development, has been shown to mediate the reparative functions of c-kit+ progenitor cells (CPCs). However, it is unclear how each of the four canonical Notch-activating ligands affects intracellular processes in c-kit+ cells when used as an external stimulus. Neonatal c-kit+ CPCs were stimulated using four different chimeric Notch-activating ligands tethered to Dynabeads, and the resulting changes were assessed using TaqMan gene expression arrays, with subsequent analysis by principal component analysis (PCA). Additionally, functional outcomes were measured using an endothelial cell tube formation assay and MSC migration assay to assess the paracrine capacity to stimulate new vessel formation and recruit other reparative cell types to the site of injury. Gene expression data showed that stimulation with Jagged-1 is associated with the greatest pro-angiogenic gene response, including the expression of VEGF and basement membrane proteins, while the other canonical ligands, Jagged-2, Dll-1, and Dll-4, are more associated with regulatory and epigenetic changes. The functional assay showed differential responses to the four ligands in terms of angiogenesis, while none of the ligands produced a robust change in migration. These data demonstrate how the four Notch-activating ligands differentially regulate CPC gene expression and function.<\/jats:p>","DOI":"10.3390\/ijms252011182","type":"journal-article","created":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T11:19:18Z","timestamp":1729163958000},"page":"11182","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Differential Effects of Four Canonical Notch-Activating Ligands on c-Kit+ Cardiac Progenitor Cells"],"prefix":"10.3390","volume":"25","author":[{"given":"Matthew","family":"Robeson","sequence":"first","affiliation":[{"name":"Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven L.","family":"Goudy","sequence":"additional","affiliation":[{"name":"Department of Pediatric Otolaryngology, Emory University, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael E.","family":"Davis","sequence":"additional","affiliation":[{"name":"Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA"},{"name":"Children\u2019s Heart Research and Outcomes (HeRO) Center, Emory University and Children\u2019s Healthcare of Atlanta, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.46582\/jsrm.0601004","article-title":"Lin-c-Kit + BM-Derived Stem Cells Repair Infarcted Heart","volume":"6","author":"Khan","year":"2010","journal-title":"J. Stem Cells Regen. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/978-1-4939-0363-4_10","article-title":"Self-Assembling Peptide-Based Delivery of Therapeutics for Myocardial Infarction","volume":"1141","author":"Boopathy","year":"2014","journal-title":"Methods Mol. 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