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Title: | Differentiation of Human Cardiac Atrial Appendage Stem Cells into Adult Cardiomyocytes: A Role for the Wnt Pathway? | Authors: | WILLEMS, Leen Daniels, Annick FANTON, Yanick LINSEN, Loes EVENS, Lize BITO, Virginie DECLERCQ, Jeroen RUMMENS, Jean-Luc HENSEN, Karen HENDRIKX, Marc |
Issue Date: | 2020 | Publisher: | MDPI | Source: | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 21 (11) (Art N° 3931) | Abstract: | Human cardiac stem cells isolated from atrial appendages based on aldehyde dehydrogenase activity (CASCs) can be expanded in vitro and differentiate into mature cardiomyocytes. In this study, we assess whether Wnt activation stimulates human CASC proliferation, whereas Wnt inhibition induces cardiac maturation. CASCs were cultured as described before. Conventional PCR confirmed the presence of the Frizzled receptors. Small-molecule inhibitors (IWP2, C59, XAV939, and IWR1-endo) and activator (CHIR99021) of the Wnt/beta -catenin signaling pathway were applied, and the effect on beta-catenin and target genes for proliferation and differentiation was assessed by Western blot and RT-qPCR. CASCs express multiple early cardiac differentiation markers and are committed toward myocardial differentiation. They express several Frizzled receptors, suggesting a role for Wnt signaling in clonogenicity, proliferation, and differentiation. Wnt activation increases total and active beta-catenin levels. However, this does not affect CASC proliferation or clonogenicity. Wnt inhibition upregulated early cardiac markers but could not induce mature myocardial differentiation. When CASCs are committed toward myocardial differentiation, the Wnt pathway is active and can be modulated. However, despite its role in cardiogenesis and myocardial differentiation of pluripotent stem-cell populations, our data indicate that Wnt signaling has limited effects on CASC clonogenicity, proliferation, and differentiation. | Notes: | Hendrikx, M (corresponding author), UHasselt, Fac Med & Life Sci, Martelarenlaan 42, B-3500 Hasselt, Belgium. leen.willems@uhasselt.be; annick.daniels@jessazh.be; yanick.fanton@beta-cell.com; loes.linsen@uzleuven.be; lize.evens@uhasselt.be; virginie.bito@uhasselt.be; jeroen.declercq@uzleuven.be; jean-luc.rummens@jessazh.be; karen.hensen@medtronic.com; marc.hendrikx@uhasselt.be |
Other: | Hendrikx, M (corresponding author), UHasselt, Fac Med & Life Sci, Martelarenlaan 42, B-3500 Hasselt, Belgium. leen.willems@uhasselt.be; annick.daniels@jessazh.be; yanick.fanton@beta-cell.com; loes.linsen@uzleuven.be; lize.evens@uhasselt.be; virginie.bito@uhasselt.be; jeroen.declercq@uzleuven.be; jean-luc.rummens@jessazh.be; karen.hensen@medtronic.com; marc.hendrikx@uhasselt.be | Keywords: | cardiac progenitor cells;cardiac regeneration;differentiation;proliferation;Wnt pathway | Document URI: | http://hdl.handle.net/1942/32460 | ISSN: | 1661-6596 | e-ISSN: | 1422-0067 | DOI: | 10.3390/ijms21113931 | ISI #: | WOS:000543400300193 | Rights: | 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2021 |
Appears in Collections: | Research publications |
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ijms-21-03931-v2.pdf | Published version | 3.16 MB | Adobe PDF | View/Open |
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