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Many steps of the cell-fate decision remain to be elucidated, being important for cancer treatment. To explore the role of Wnt\/\u03b2-catenin for MK and RBC differentiation, we activated \u03b2-catenin signaling in platelet-derived growth factor b (Pdgfb)-expressing cells of the HS using a Cre-lox approach (Ctnnb1BM-GOF). FACS analysis revealed that Pdgfb is mainly expressed by megakaryocytic progenitors (MKPs), MKs and platelets. Recombination resulted in a lethal phenotype in mutants (Ctnnb1BM-GOFwt\/fl, Ctnnb1BM-GOFfl\/fl) 3 weeks after tamoxifen injection, showing an increase in MKs in the BM and spleen, but no pronounced anemia despite reduced erythrocyte counts. BM transplantation (BMT) of Ctnnb1BM-GOF BM into lethally irradiated wildtype recipients (BMT-Ctnnb1BM-GOF) confirmed the megakaryocytic, but not the lethal phenotype. CFU-MK assays in vitro with BM cells of Ctnnb1BM-GOF mice supported MK skewing at the expense of erythroid colonies. Molecularly, the runt-related transcription factor 1 (RUNX1) mRNA, known to suppress erythropoiesis, was upregulated in Ctnnb1BM-GOF BM cells. In conclusion, \u03b2-catenin activation plays a key role in cell-fate decision favoring MK development at the expense of erythroid production.<\/jats:p>","DOI":"10.3390\/cells12232765","type":"journal-article","created":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T05:28:21Z","timestamp":1701667701000},"page":"2765","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Wnt\/\u03b2-Catenin-Signaling Modulates Megakaryopoiesis at the Megakaryocyte-Erythrocyte Progenitor Stage in the Hematopoietic System"],"prefix":"10.3390","volume":"12","author":[{"given":"Burak H.","family":"Yalcin","sequence":"first","affiliation":[{"name":"Institute of Neurology (Edinger Institute), University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jadranka","family":"Macas","sequence":"additional","affiliation":[{"name":"Institute of Neurology (Edinger Institute), University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8434-6492","authenticated-orcid":false,"given":"Eliza","family":"Wiercinska","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine and Immunohaematology, and DRK-Blutspendedienst BaW\u00fcHe, Goethe University Frankfurt, 60528 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick N.","family":"Harter","sequence":"additional","affiliation":[{"name":"Institute of Neurology (Edinger Institute), University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malak","family":"Fawaz","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology\/Oncology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessa","family":"Schmachtel","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology\/Oncology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Ghiro","sequence":"additional","affiliation":[{"name":"Institute of Neurology (Edinger Institute), University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Bieniek","sequence":"additional","affiliation":[{"name":"German Center for Lung Research (DZL), Department of Internal Medicine, Excellence Cluster Cardio-Pulmonary Institute (CPI), Justus Liebig University of Giessen, Aulweg 130, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djuro","family":"Kosanovic","sequence":"additional","affiliation":[{"name":"German Center for Lung Research (DZL), Department of Internal Medicine, Excellence Cluster Cardio-Pulmonary Institute (CPI), Justus Liebig University of Giessen, Aulweg 130, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Thom","sequence":"additional","affiliation":[{"name":"Institute of Neurology (Edinger Institute), University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6962-5485","authenticated-orcid":false,"given":"Marcus","family":"Fruttiger","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto M.","family":"Taketo","sequence":"additional","affiliation":[{"name":"Kyoto University Hospital-iACT Graduate School of Medicine, Kyoto University, Kyoto 06-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5167-6970","authenticated-orcid":false,"given":"Ralph T.","family":"Schermuly","sequence":"additional","affiliation":[{"name":"German Center for Lung Research (DZL), Department of Internal Medicine, Excellence Cluster Cardio-Pulmonary Institute (CPI), Justus Liebig University of Giessen, Aulweg 130, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Rieger","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology\/Oncology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany"},{"name":"German Cancer Consortium (DKTK) at the German Cancer Research Center, 69120 Heidelberg, Germany"},{"name":"Frankfurt Cancer Institute (FCI), 60596 Frankfurt am Main, Germany"},{"name":"Excellence Cluster Cardio-Pulmonary Institute (CPI), Partner Site Frankfurt, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl H.","family":"Plate","sequence":"additional","affiliation":[{"name":"Institute of Neurology (Edinger Institute), University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany"},{"name":"Frankfurt Cancer Institute (FCI), 60596 Frankfurt am Main, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Frankfurt\/Mainz, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halvard","family":"Bonig","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine and Immunohaematology, and DRK-Blutspendedienst BaW\u00fcHe, Goethe University Frankfurt, 60528 Frankfurt am Main, Germany"},{"name":"Department of Medicine\/Division of Hematology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Liebner","sequence":"additional","affiliation":[{"name":"Institute of Neurology (Edinger Institute), University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany"},{"name":"Excellence Cluster Cardio-Pulmonary Institute (CPI), Partner Site Frankfurt, 60590 Frankfurt am Main, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Frankfurt\/Mainz, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/cyto.a.20674","article-title":"Mouse Hematopoietic Stem Cell Identification and Analysis","volume":"75A","author":"Challen","year":"2009","journal-title":"Cytom. 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