{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T21:29:39Z","timestamp":1772227779695,"version":"3.50.1"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T00:00:00Z","timestamp":1685059200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T00:00:00Z","timestamp":1685059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82100321"],"award-info":[{"award-number":["82100321"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81670290"],"award-info":[{"award-number":["81670290"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970324"],"award-info":[{"award-number":["81970324"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81974019"],"award-info":[{"award-number":["81974019"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010031","name":"Postdoctoral Research Foundation of China","doi-asserted-by":"publisher","award":["2020M682642"],"award-info":[{"award-number":["2020M682642"]}],"id":[{"id":"10.13039\/501100010031","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012245","name":"Science and Technology Planning Project of Guangdong Province","doi-asserted-by":"publisher","award":["2019B020230003"],"award-info":[{"award-number":["2019B020230003"]}],"id":[{"id":"10.13039\/501100012245","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012245","name":"Science and Technology Planning Project of Guangdong Province","doi-asserted-by":"publisher","award":["2018B090944002"],"award-info":[{"award-number":["2018B090944002"]}],"id":[{"id":"10.13039\/501100012245","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012245","name":"Science and Technology Planning Project of Guangdong Province","doi-asserted-by":"publisher","award":["2020B1111170011"],"award-info":[{"award-number":["2020B1111170011"]}],"id":[{"id":"10.13039\/501100012245","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012245","name":"Science and Technology Planning Project of Guangdong Province","doi-asserted-by":"publisher","award":["2022B1212010010"],"award-info":[{"award-number":["2022B1212010010"]}],"id":[{"id":"10.13039\/501100012245","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Program of Guangzhou Science Research Plan","award":["201904020047"],"award-info":[{"award-number":["201904020047"]}]},{"name":"Technology Program of Guangzhou","award":["202206010049"],"award-info":[{"award-number":["202206010049"]}]},{"name":"Guangdong Peak Project","award":["DFJH201802"],"award-info":[{"award-number":["DFJH201802"]}]},{"name":"National Key Research and Development Program of China","award":["2018YFA0108700"],"award-info":[{"award-number":["2018YFA0108700"]}]},{"name":"National Key Research and Development Program of China","award":["2017YFA0105602"],"award-info":[{"award-number":["2017YFA0105602"]}]},{"name":"NSFC Projects of International Cooperation and Exchanges","award":["81720108004"],"award-info":[{"award-number":["81720108004"]}]},{"name":"Research Team Project of Natural Science Foundation of Guangdong Province of China","award":["2017A030312007"],"award-info":[{"award-number":["2017A030312007"]}]},{"name":"Special Project of Dengfeng Program of Guangdong Provincial People's Hospital","award":["DFJH201812"],"award-info":[{"award-number":["DFJH201812"]}]},{"name":"Special Project of Dengfeng Program of Guangdong Provincial People's Hospital","award":["KJ012019119"],"award-info":[{"award-number":["KJ012019119"]}]},{"name":"Special Project of Dengfeng Program of Guangdong Provincial People's Hospital","award":["KJ012019423"],"award-info":[{"award-number":["KJ012019423"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Tissue Res"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Human umbilical cord\u2013derived mesenchymal stem cells (hUC-MSCs) are used to regenerate the myocardium during cardiac repair after myocardial infarction. However, the regulatory mechanism underlying their ability to form mesodermal cells and differentiate into cardiomyocytes remains unclear. Here, we established a human-derived MSCs line isolated from healthy umbilical cords and established a cell model of the natural state to examine the differentiation of hUC-MSCs into cardiomyocytes. Quantitative RT-PCR, western blotting, immunofluorescence, flow cytometry, RNA Seq, and inhibitors of canonical Wnt signalling were used to detect the germ-layer markers <jats:italic>T<\/jats:italic> and <jats:italic>MIXL1<\/jats:italic>; the markers of cardiac progenitor cells <jats:italic>MESP1<\/jats:italic>, <jats:italic>GATA4<\/jats:italic>, and <jats:italic>NKX2.5<\/jats:italic> and the cardiomyocyte-marker cTnT to identify the molecular mechanism associated with PYGO2, a key component of the canonical Wnt signalling pathway that regulates the formation of cardiomyocyte-like cells. We demonstrated that PYGO2 promotes the formation of mesodermal-like cells and their differentiation into cardiomyocytes through the hUC-MSC-dependent canonical Wnt signalling by promoting the early-stage entry of \u03b2-catenin into the nucleus. Surprisingly, PYGO2 did not alter the expression of the canonical-Wnt, NOTCH, or BMP signalling pathways during the middle\u2013late stages. In contrast, PI3K-Akt signalling promoted hUC-MSCs formation and their differentiation into cardiomyocyte-like cells. To the best of our knowledge, this is the first study to demonstrate that PYGO2 uses a biphasic mechanism to promote cardiomyocyte formation from hUC-MSCs.<\/jats:p>","DOI":"10.1007\/s00441-023-03774-6","type":"journal-article","created":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T05:02:41Z","timestamp":1685077361000},"page":"163-179","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Novel biphasic mechanism of the canonical Wnt signalling component PYGO2 promotes cardiomyocyte differentiation from hUC-MSCs"],"prefix":"10.1007","volume":"393","author":[{"given":"Yan","family":"Shi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Qin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiongwei","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongqing","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuequn","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wuzhou","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhigang","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jimei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongqi","family":"Wan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8431-4266","authenticated-orcid":false,"given":"Xiushan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,5,26]]},"reference":[{"key":"3774_CR1","doi-asserted-by":"publisher","first-page":"4089","DOI":"10.1242\/dev.129.17.4089","volume":"129","author":"TY Belenkaya","year":"2002","unstructured":"Belenkaya TY, Han C, Standley HJ, Lin X, Houston DW, Heasman J, Lin X (2002) pygopus Encodes a nuclear protein essential for wingless\/Wnt signaling. Development 129:4089\u20134101. https:\/\/doi.org\/10.1242\/dev.129.17.4089","journal-title":"Development"},{"key":"3774_CR2","doi-asserted-by":"publisher","first-page":"e146","DOI":"10.1161\/cir.0000000000000485","volume":"135","author":"EJ Benjamin","year":"2017","unstructured":"Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, de Ferranti SD, Floyd J, Fornage M, Gillespie C, Isasi CR, Jim\u00e9nez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Mackey RH, Matsushita K, Mozaffarian D, Mussolino ME, Nasir K, Neumar RW, Palaniappan L, Pandey DK, Thiagarajan RR, Reeves MJ, Ritchey M, Rodriguez CJ, Roth GA, Rosamond WD, Sasson C, Towfighi A, Tsao CW, Turner MB, Virani SS, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P (2017) Heart disease and stroke statistics\u20142017 update: a report from the American Heart Association. Circulation 135:e146\u2013e603. https:\/\/doi.org\/10.1161\/cir.0000000000000485","journal-title":"Circulation"},{"key":"3774_CR3","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.ydbio.2014.11.015","volume":"398","author":"JA Bisson","year":"2015","unstructured":"Bisson JA, Mills B, Paul Helt JC, Zwaka TP, Cohen ED (2015) Wnt5a and Wnt11 inhibit the canonical Wnt pathway and promote cardiac progenitor development via the Caspase-dependent degradation of AKT. Dev Biol 398:80\u201396. https:\/\/doi.org\/10.1016\/j.ydbio.2014.11.015","journal-title":"Dev Biol"},{"key":"3774_CR4","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.stem.2020.06.001","volume":"27","author":"JW Buikema","year":"2020","unstructured":"Buikema JW, Lee S, Goodyer WR, Maas RG, Chirikian O, Li G, Miao Y, Paige SL, Lee D, Wu H, Paik DT, Rhee S, Tian L, Galdos FX, Puluca N, Beyersdorf B, Hu J, Beck A, Venkamatran S, Swami S, Wijnker P, Schuldt M, Dorsch LM, van Mil A, Red-Horse K, Wu JY, Geisen C, Hesse M, Serpooshan V, Jovinge S, Fleischmann BK, Doevendans PA, van der Velden J, Garcia KC, Wu JC, Sluijter JPG, Wu SM (2020) Wnt activation and reduced cell-cell contact synergistically induce massive expansion of functional human iPSC-derived cardiomyocytes. Cell Stem Cell 27:50-63.e5. https:\/\/doi.org\/10.1016\/j.stem.2020.06.001","journal-title":"Cell Stem Cell"},{"key":"3774_CR5","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1146\/annurev-genet-112414-054911","volume":"49","author":"PW Burridge","year":"2015","unstructured":"Burridge PW, Sharma A, Wu JC (2015) Genetic and epigenetic regulation of human cardiac reprogramming and differentiation in regenerative medicine. Annu Rev Genet 49:461\u2013484. https:\/\/doi.org\/10.1146\/annurev-genet-112414-054911","journal-title":"Annu Rev Genet"},{"key":"3774_CR6","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1101\/gad.315531.118","volume":"32","author":"C Cant\u00f9","year":"2018","unstructured":"Cant\u00f9 C, Felker A, Zimmerli D, Prummel KD, Cabello EM, Chiavacci E, M\u00e9ndez-Acevedo KM, Kirchgeorg L, Burger S, Ripoll J, Valenta T, Hausmann G, Vilain N, Aguet M, Burger A, Pan\u00e1kov\u00e1 D, Basler K, Mosimann C (2018) Mutations in Bcl9 and Pygo genes cause congenital heart defects by tissue-specific perturbation of Wnt\/\u03b2-catenin signaling. Genes Dev 32:1443\u20131458. https:\/\/doi.org\/10.1101\/gad.315531.118","journal-title":"Genes Dev"},{"key":"3774_CR7","doi-asserted-by":"publisher","unstructured":"Cant\u00f9 C, Pagella P, Shajiei TD, Zimmerli D, Valenta T, Hausmann G, Basler K, Mitsiadis TA\u00a0(2017) A cytoplasmic role of Wnt\/\u03b2-catenin transcriptional cofactors Bcl9, Bcl9l, and Pygopus in tooth enamel formation. Sci Signal 10. https:\/\/doi.org\/10.1126\/scisignal.aah4598","DOI":"10.1126\/scisignal.aah4598"},{"key":"3774_CR8","doi-asserted-by":"publisher","first-page":"2377","DOI":"10.1242\/dev.093591","volume":"140","author":"C Cant\u00f9","year":"2013","unstructured":"Cant\u00f9 C, Valenta T, Hausmann G, Vilain N, Aguet M, Basler K (2013) The Pygo2-H3K4me2\/3 interaction is dispensable for mouse development and Wnt signaling-dependent transcription. Development 140:2377\u20132386. https:\/\/doi.org\/10.1242\/dev.093591","journal-title":"Development"},{"key":"3774_CR9","doi-asserted-by":"publisher","first-page":"1879","DOI":"10.1101\/gad.246140.114","volume":"28","author":"C Cant\u00f9","year":"2014","unstructured":"Cant\u00f9 C, Zimmerli D, Hausmann G, Valenta T, Moor A, Aguet M, Basler K (2014) Pax6-dependent, but \u03b2-catenin-independent, function of Bcl9 proteins in mouse lens development. Genes Dev 28:1879\u20131884. https:\/\/doi.org\/10.1101\/gad.246140.114","journal-title":"Genes Dev"},{"key":"3774_CR10","doi-asserted-by":"publisher","first-page":"5621","DOI":"10.1128\/mcb.00465-10","volume":"30","author":"J Chen","year":"2010","unstructured":"Chen J, Luo Q, Yuan Y, Huang X, Cai W, Li C, Wei T, Zhang L, Yang M, Liu Q, Ye G, Dai X, Li B (2010) Pygo2 associates with MLL2 histone methyltransferase and GCN5 histone acetyltransferase complexes to augment Wnt target gene expression and breast cancer stem-like cell expansion. Mol Cell Biol 30:5621\u20135635. https:\/\/doi.org\/10.1128\/mcb.00465-10","journal-title":"Mol Cell Biol"},{"key":"3774_CR11","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1016\/j.jcyt.2019.04.056","volume":"21","author":"M Colicchia","year":"2019","unstructured":"Colicchia M, Jones DA, Beirne AM, Hussain M, Weeraman D, Rathod K, Veerapen J, Lowdell M, Mathur A (2019) Umbilical cord-derived mesenchymal stromal cells in cardiovascular disease: review of preclinical and clinical data. Cytotherapy 21:1007\u20131018. https:\/\/doi.org\/10.1016\/j.jcyt.2019.04.056","journal-title":"Cytotherapy"},{"key":"3774_CR12","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.cub.2007.01.063","volume":"17","author":"M de la Roche","year":"2007","unstructured":"de la Roche M, Bienz M (2007) Wingless-independent association of Pygopus with dTCF target genes. Curr Biol 17:556\u2013561. https:\/\/doi.org\/10.1016\/j.cub.2007.01.063","journal-title":"Curr Biol"},{"key":"3774_CR13","doi-asserted-by":"publisher","unstructured":"Fiedler M, Graeb M, Mieszczanek J, Rutherford TJ, Johnson CM, Bienz M\u00a0(2015) An ancient Pygo-dependent Wnt enhanceosome integrated by Chip\/LDB-SSDP. Elife 4. https:\/\/doi.org\/10.7554\/eLife.09073","DOI":"10.7554\/eLife.09073"},{"key":"3774_CR14","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD007888.pub2,Cd007888.10.1002\/14651858.CD007888.pub2","author":"SA Fisher","year":"2014","unstructured":"Fisher SA, Brunskill SJ, Doree C, Mathur A, Taggart DP, Martin-Rendon E (2014) Stem cell therapy for chronic ischaemic heart disease and congestive heart failure. Cochrane Database Syst Rev. https:\/\/doi.org\/10.1002\/14651858.CD007888.pub2,Cd007888.10.1002\/14651858.CD007888.pub2","journal-title":"Cochrane Database Syst Rev"},{"key":"3774_CR15","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1101\/gad.1279405","volume":"19","author":"AC Foley","year":"2005","unstructured":"Foley AC, Mercola M (2005) Heart induction by Wnt antagonists depends on the homeodomain transcription factor Hex. Genes Dev 19:387\u2013396. https:\/\/doi.org\/10.1101\/gad.1279405","journal-title":"Genes Dev"},{"key":"3774_CR16","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1124\/pr.117.013896","volume":"70","author":"S Foulquier","year":"2018","unstructured":"Foulquier S, Daskalopoulos EP, Lluri G, Hermans KCM, Deb A, Blankesteijn WM (2018) WNT signaling in cardiac and vascular disease. Pharmacol Rev 70:68\u2013141. https:\/\/doi.org\/10.1124\/pr.117.013896","journal-title":"Pharmacol Rev"},{"key":"3774_CR17","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1186\/s12916-015-0399-z","volume":"13","author":"LR Gao","year":"2015","unstructured":"Gao LR, Chen Y, Zhang NK, Yang XL, Liu HL, Wang ZG, Yan XY, Wang Y, Zhu ZM, Li TC, Wang LH, Chen HY, Chen YD, Huang CL, Qu P, Yao C, Wang B, Chen GH, Wang ZM, Xu ZY, Bai J, Lu D, Shen YH, Guo F, Liu MY, Yang Y, Ding YC, Yang Y, Tian HT, Ding QA, Li LN, Yang XC, Hu X (2015) Intracoronary infusion of Wharton\u2019s jelly-derived mesenchymal stem cells in acute myocardial infarction: double-blind, randomized controlled trial. BMC Med 13:162. https:\/\/doi.org\/10.1186\/s12916-015-0399-z","journal-title":"BMC Med"},{"key":"3774_CR18","doi-asserted-by":"publisher","first-page":"1384","DOI":"10.1016\/j.ygeno.2019.08.007","volume":"112","author":"K Govarthanan","year":"2020","unstructured":"Govarthanan K, Gupta PK, Ramasamy D, Kumar P, Mahadevan S, Verma RS (2020) DNA methylation microarray uncovers a permissive methylome for cardiomyocyte differentiation in human mesenchymal stem cells. Genomics 112:1384\u20131395. https:\/\/doi.org\/10.1016\/j.ygeno.2019.08.007","journal-title":"Genomics"},{"key":"3774_CR19","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.stem.2013.04.012","volume":"13","author":"B Gu","year":"2013","unstructured":"Gu B, Watanabe K, Sun P, Fallahi M, Dai X (2013) Chromatin effector Pygo2 mediates Wnt-notch crosstalk to suppress luminal\/alveolar potential of mammary stem and basal cells. Cell Stem Cell 13:48\u201361. https:\/\/doi.org\/10.1016\/j.stem.2013.04.012","journal-title":"Cell Stem Cell"},{"key":"3774_CR20","doi-asserted-by":"publisher","first-page":"1666","DOI":"10.1007\/s12015-021-10168-0","volume":"17","author":"S Gupta","year":"2021","unstructured":"Gupta S, Sharma A, S, A. & Verma, R. S. (2021) Mesenchymal stem cells for cardiac regeneration: from differentiation to cell delivery. Stem Cell Rev Rep 17:1666\u20131694. https:\/\/doi.org\/10.1007\/s12015-021-10168-0","journal-title":"Stem Cell Rev Rep"},{"key":"3774_CR21","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1083\/jcb.148.3.567","volume":"148","author":"J Huelsken","year":"2000","unstructured":"Huelsken J, Vogel R, Brinkmann V, Erdmann B, Birchmeier C, Birchmeier W (2000) Requirement for beta-catenin in anterior-posterior axis formation in mice. J Cell Biol 148:567\u2013578. https:\/\/doi.org\/10.1083\/jcb.148.3.567","journal-title":"J Cell Biol"},{"key":"3774_CR22","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1016\/j.ydbio.2008.03.014","volume":"318","author":"N Jonckheere","year":"2008","unstructured":"Jonckheere N, Mayes E, Shih HP, Li B, Lioubinski O, Dai X, Sander M (2008) Analysis of mPygo2 mutant mice suggests a requirement for mesenchymal Wnt signaling in pancreatic growth and differentiation. Dev Biol 318:224\u2013235. https:\/\/doi.org\/10.1016\/j.ydbio.2008.03.014","journal-title":"Dev Biol"},{"key":"3774_CR23","doi-asserted-by":"publisher","first-page":"3303","DOI":"10.1002\/jbm.a.36530","volume":"106","author":"J Joshi","year":"2018","unstructured":"Joshi J, Brennan D, Beachley V, Kothapalli CR (2018) Cardiomyogenic differentiation of human bone marrow-derived mesenchymal stem cell spheroids within electrospun collagen nanofiber mats. J Biomed Mater Res A 106:3303\u20133312. https:\/\/doi.org\/10.1002\/jbm.a.36530","journal-title":"J Biomed Mater Res A"},{"key":"3774_CR24","doi-asserted-by":"publisher","first-page":"10894","DOI":"10.1073\/pnas.0704044104","volume":"104","author":"C Kwon","year":"2007","unstructured":"Kwon C, Arnold J, Hsiao EC, Taketo MM, Conklin BR, Srivastava D (2007) Canonical Wnt signaling is a positive regulator of mammalian cardiac progenitors. Proc Natl Acad Sci U S A 104:10894\u201310899. https:\/\/doi.org\/10.1073\/pnas.0704044104","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3774_CR25","doi-asserted-by":"publisher","first-page":"1858","DOI":"10.1002\/stem.124","volume":"27","author":"MY Lee","year":"2009","unstructured":"Lee MY, Lim HW, Lee SH, Han HJ (2009) Smad, PI3K\/Akt, and Wnt-dependent signaling pathways are involved in BMP-4-induced ESC self-renewal. Stem Cells 27:1858\u20131868. https:\/\/doi.org\/10.1002\/stem.124","journal-title":"Stem Cells"},{"key":"3774_CR26","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1016\/j.ygeno.2004.04.007","volume":"84","author":"B Li","year":"2004","unstructured":"Li B, Mackay DR, Ma J, Dai X (2004) Cloning and developmental expression of mouse pygopus 2, a putative Wnt signaling component. Genomics 84:398\u2013405. https:\/\/doi.org\/10.1016\/j.ygeno.2004.04.007","journal-title":"Genomics"},{"key":"3774_CR27","doi-asserted-by":"publisher","first-page":"E1848","DOI":"10.1073\/pnas.1200250109","volume":"109","author":"X Lian","year":"2012","unstructured":"Lian X, Hsiao C, Wilson G, Zhu K, Hazeltine LB, Azarin SM, Raval KK, Zhang J, Kamp TJ, Palecek SP (2012) Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. Proc Natl Acad Sci U S A 109:E1848\u2013E1857. https:\/\/doi.org\/10.1073\/pnas.1200250109","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3774_CR28","doi-asserted-by":"publisher","first-page":"H1634","DOI":"10.1152\/ajpheart.00538.2020","volume":"320","author":"L Lin","year":"2021","unstructured":"Lin L, Xu W, Li Y, Zhu P, Yuan W, Liu M, Shi Y, Chen Y, Liang J, Chen J, Yang B, Cai W, Wen Y, Zhu X, Peng X, Zhou Z, Mo X, Wan Y, Yuan H, Li F, Ye X, Jiang Z, Wang Y, Zhuang J, Fan X, Wu X (2021) Pygo1 regulates pathological cardiac hypertrophy via a \u03b2-catenin-dependent mechanism. Am J Physiol Heart Circ Physiol 320:H1634-h1645. https:\/\/doi.org\/10.1152\/ajpheart.00538.2020","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"3774_CR29","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1038\/11932","volume":"22","author":"P Liu","year":"1999","unstructured":"Liu P, Wakamiya M, Shea MJ, Albrecht U, Behringer RR, Bradley A (1999) Requirement for Wnt3 in vertebrate axis formation. Nat Genet 22:361\u2013365. https:\/\/doi.org\/10.1038\/11932","journal-title":"Nat Genet"},{"key":"3774_CR30","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s13287-017-0472-y","volume":"8","author":"C Mao","year":"2017","unstructured":"Mao C, Hou X, Wang B, Chi J, Jiang Y, Zhang C, Li Z (2017) Intramuscular injection of human umbilical cord-derived mesenchymal stem cells improves cardiac function in dilated cardiomyopathy rats. Stem Cell Res Ther 8:18. https:\/\/doi.org\/10.1186\/s13287-017-0472-y","journal-title":"Stem Cell Res Ther"},{"key":"3774_CR31","doi-asserted-by":"publisher","first-page":"8242","DOI":"10.1038\/s41598-021-87547-7","volume":"11","author":"C Markouli","year":"2021","unstructured":"Markouli C, De Deckersberg EC, Dziedzicka D, Regin M, Franck S, Keller A, Gheldof A, Geens M, Sermon K, Spits C (2021) Sustained intrinsic WNT and BMP4 activation impairs hESC differentiation to definitive endoderm and drives the cells towards extra-embryonic mesoderm. Sci Rep 11:8242. https:\/\/doi.org\/10.1038\/s41598-021-87547-7","journal-title":"Sci Rep"},{"key":"3774_CR32","doi-asserted-by":"publisher","first-page":"3087","DOI":"10.1089\/scd.2013.0119","volume":"22","author":"EC Martinez","year":"2013","unstructured":"Martinez EC, Vu DT, Wang J, Lilyanna S, Ling LH, Gan SU, Tan AL, Phan TT, Lee CN, Kofidis T (2013) Grafts enriched with subamnion-cord-lining mesenchymal stem cell angiogenic spheroids induce post-ischemic myocardial revascularization and preserve cardiac function in failing rat hearts. Stem Cells Dev 22:3087\u20133099. https:\/\/doi.org\/10.1089\/scd.2013.0119","journal-title":"Stem Cells Dev"},{"key":"3774_CR33","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1101\/gad.855501","volume":"15","author":"MJ Marvin","year":"2001","unstructured":"Marvin MJ, Di Rocco G, Gardiner A, Bush SM, Lassar AB (2001) Inhibition of Wnt activity induces heart formation from posterior mesoderm. Genes Dev 15:316\u2013327. https:\/\/doi.org\/10.1101\/gad.855501","journal-title":"Genes Dev"},{"key":"3774_CR34","doi-asserted-by":"publisher","first-page":"2208","DOI":"10.1016\/j.str.2013.09.013","volume":"21","author":"TC Miller","year":"2013","unstructured":"Miller TC, Mieszczanek J, S\u00e1nchez-Barrena MJ, Rutherford TJ, Fiedler M, Bienz M (2013) Evolutionary adaptation of the fly Pygo PHD finger toward recognizing histone H3 tail methylated at arginine 2. Structure 21:2208\u20132220. https:\/\/doi.org\/10.1016\/j.str.2013.09.013","journal-title":"Structure"},{"key":"3774_CR35","doi-asserted-by":"publisher","first-page":"195","DOI":"10.4252\/wjsc.v6.i2.195","volume":"6","author":"T Nagamura-Inoue","year":"2014","unstructured":"Nagamura-Inoue T, He H (2014) Umbilical cord-derived mesenchymal stem cells: their advantages and potential clinical utility. World J Stem Cells 6:195\u2013202. https:\/\/doi.org\/10.4252\/wjsc.v6.i2.195","journal-title":"World J Stem Cells"},{"key":"3774_CR36","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1016\/j.ydbio.2008.05.553","volume":"320","author":"M Nair","year":"2008","unstructured":"Nair M, Nagamori I, Sun P, Mishra DP, Rh\u00e9aume C, Li B, Sassone-Corsi P, Dai X (2008) Nuclear regulator Pygo2 controls spermiogenesis and histone H3 acetylation. Dev Biol 320:446\u2013455. https:\/\/doi.org\/10.1016\/j.ydbio.2008.05.553","journal-title":"Dev Biol"},{"key":"3774_CR37","doi-asserted-by":"publisher","unstructured":"Pedone E, Failli M, Gambardella G, De Cegli R, La Regina A, di Bernardo D, Marucci L\u00a0(2022) \u03b2-catenin perturbations control differentiation programs in mouse embryonic stem cells. iScience 25:103756. https:\/\/doi.org\/10.1016\/j.isci.2022.103756","DOI":"10.1016\/j.isci.2022.103756"},{"key":"3774_CR38","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1007\/s10616-014-9812-2","volume":"68","author":"TL Pham","year":"2016","unstructured":"Pham TL, Nguyen TT, Van Bui A, Nguyen MT, Van Pham P (2016) Fetal heart extract facilitates the differentiation of human umbilical cord blood-derived mesenchymal stem cells into heart muscle precursor cells. Cytotechnology 68:645\u2013658. https:\/\/doi.org\/10.1007\/s10616-014-9812-2","journal-title":"Cytotechnology"},{"key":"3774_CR39","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.stem.2019.07.010","volume":"25","author":"SI Protze","year":"2019","unstructured":"Protze SI, Lee JH, Keller GM (2019) Human pluripotent stem cell-derived cardiovascular cells: from developmental biology to therapeutic applications. Cell Stem Cell 25:311\u2013327. https:\/\/doi.org\/10.1016\/j.stem.2019.07.010","journal-title":"Cell Stem Cell"},{"key":"3774_CR40","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1007\/s12015-021-10165-3","volume":"17","author":"S Ramesh","year":"2021","unstructured":"Ramesh S, Govarthanan K, Ostrovidov S, Zhang H, Hu Q, Camci-Unal G, Verma RS, Ramalingam M (2021) Cardiac differentiation of mesenchymal stem cells: impact of biological and chemical inducers. Stem Cell Rev Rep 17:1343\u20131361. https:\/\/doi.org\/10.1007\/s12015-021-10165-3","journal-title":"Stem Cell Rev Rep"},{"key":"3774_CR41","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/j.biopha.2018.10.065","volume":"109","author":"R Rikhtegar","year":"2019","unstructured":"Rikhtegar R, Pezeshkian M, Dolati S, Safaie N, Afrasiabi Rad A, Mahdipour M, Nouri M, Jodati AR, Yousefi M (2019) Stem cells as therapy for heart disease: iPSCs, ESCs, CSCs, and skeletal myoblasts. Biomed Pharmacother 109:304\u2013313. https:\/\/doi.org\/10.1016\/j.biopha.2018.10.065","journal-title":"Biomed Pharmacother"},{"key":"3774_CR42","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.biopha.2016.01.020","volume":"78","author":"Z Ruan","year":"2016","unstructured":"Ruan Z, Zhu L, Yin Y, Chen G (2016) Overexpressing NKx2.5 increases the differentiation of human umbilical cord drived mesenchymal stem cells into cardiomyocyte-like cells. Biomed Pharmacother 78:110\u2013115. https:\/\/doi.org\/10.1016\/j.biopha.2016.01.020","journal-title":"Biomed Pharmacother"},{"key":"3774_CR43","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/scrt394","volume":"5","author":"D Santos Nascimento","year":"2014","unstructured":"Santos Nascimento D, Mosqueira D, Sousa LM, Teixeira M, Filipe M, Resende TP, Ara\u00fajo AF, Valente M, Almeida J, Martins JP, Santos JM, B\u00e1rcia RN, Cruz P, Cruz H, Pinto-do-\u00d3 P (2014) Human umbilical cord tissue-derived mesenchymal stromal cells attenuate remodeling after myocardial infarction by proangiogenic, antiapoptotic, and endogenous cell-activation mechanisms. Stem Cell Res Ther 5:5. https:\/\/doi.org\/10.1186\/scrt394","journal-title":"Stem Cell Res Ther"},{"key":"3774_CR44","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/1741-7007-5-15","volume":"5","author":"KR Schwab","year":"2007","unstructured":"Schwab KR, Patterson LT, Hartman HA, Song N, Lang RA, Lin X, Potter SS (2007) Pygo1 and Pygo2 roles in Wnt signaling in mammalian kidney development. BMC Biol 5:15. https:\/\/doi.org\/10.1186\/1741-7007-5-15","journal-title":"BMC Biol"},{"key":"3774_CR45","doi-asserted-by":"publisher","first-page":"14167","DOI":"10.1038\/s41598-020-70806-4","volume":"10","author":"Y Shi","year":"2020","unstructured":"Shi Y, Li Y, Wang Y, Zhu P, Chen Y, Wang H, Yue S, Xia X, Chen J, Jiang Z, Zhou C, Cai W, Yuan H, Wu Y, Wan Y, Li X, Zhu X, Zhou Z, Dai G, Li F, Mo X, Ye X, Fan X, Zhuang J, Wu X, Yuan W (2020a) BVES downregulation in non-syndromic tetralogy of fallot is associated with ventricular outflow tract stenosis. Sci Rep 10:14167. https:\/\/doi.org\/10.1038\/s41598-020-70806-4","journal-title":"Sci Rep"},{"key":"3774_CR46","doi-asserted-by":"publisher","first-page":"1084006","DOI":"10.1155\/2022\/1084006","volume":"2022","author":"Y Shi","year":"2022","unstructured":"Shi Y, Wang S, Yang R, Wang Z, Zhang W, Liu H, Huang Y (2022) ROS promote hypoxia-induced keratinocyte epithelial-mesenchymal transition by inducing SOX2 expression and subsequent activation of Wnt\/\u03b2-catenin. Oxid Med Cell Longev 2022:1084006. https:\/\/doi.org\/10.1155\/2022\/1084006","journal-title":"Oxid Med Cell Longev"},{"key":"3774_CR47","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1042\/bst20200393","volume":"48","author":"Y Shi","year":"2020","unstructured":"Shi Y, Wu X, Zhu S, Huang H, Zhuang J, Yuan H, Yuan W, Zhu P (2020b) Structure and function of Pygo in organ development dependent and independent Wnt signalling. Biochem Soc Trans 48:1781\u20131794. https:\/\/doi.org\/10.1042\/bst20200393","journal-title":"Biochem Soc Trans"},{"key":"3774_CR48","doi-asserted-by":"publisher","first-page":"1873","DOI":"10.1242\/dev.001495","volume":"134","author":"N Song","year":"2007","unstructured":"Song N, Schwab KR, Patterson LT, Yamaguchi T, Lin X, Potter SS, Lang RA (2007) pygopus 2 has a crucial, Wnt pathway-independent function in lens induction. Development 134:1873\u20131885. https:\/\/doi.org\/10.1242\/dev.001495","journal-title":"Development"},{"key":"3774_CR49","doi-asserted-by":"publisher","unstructured":"Sun Y, Liu J, Xu Z, Lin X, Zhang X, Li L, Li Y\u00a0(2020) Matrix stiffness regulates myocardial differentiation of human umbilical cord mesenchymal stem cells. Aging (Albany NY) 13:2231\u20132250. https:\/\/doi.org\/10.18632\/aging.202244","DOI":"10.18632\/aging.202244"},{"key":"3774_CR50","doi-asserted-by":"publisher","unstructured":"Szemes M, Melegh Z, Bellamy J, Greenhough A, Kollareddy M, Catchpoole D, Malik K\u00a0(2020) A Wnt-BMP4 signaling axis induces MSX and NOTCH proteins and promotes growth suppression and differentiation in neuroblastoma. Cells 9. https:\/\/doi.org\/10.3390\/cells9030783","DOI":"10.3390\/cells9030783"},{"key":"3774_CR51","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1002\/dvg.22724","volume":"52","author":"M Tang","year":"2014","unstructured":"Tang M, Yuan W, Bodmer R, Wu X, Ocorr K (2014) The role of pygopus in the differentiation of intracardiac valves in Drosophila. Genesis 52:19\u201328. https:\/\/doi.org\/10.1002\/dvg.22724","journal-title":"Genesis"},{"key":"3774_CR52","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1161\/circgenetics.113.000253","volume":"6","author":"M Tang","year":"2013","unstructured":"Tang M, Yuan W, Fan X, Liu M, Bodmer R, Ocorr K, Wu X (2013) Pygopus maintains heart function in aging Drosophila independently of canonical Wnt signaling. Circ Cardiovasc Genet 6:472\u2013480. https:\/\/doi.org\/10.1161\/circgenetics.113.000253","journal-title":"Circ Cardiovasc Genet"},{"key":"3774_CR53","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1038\/ncb1141","volume":"6","author":"FM Townsley","year":"2004","unstructured":"Townsley FM, Cliffe A, Bienz M (2004) Pygopus and Legless target Armadillo\/beta-catenin to the nucleus to enable its transcriptional co-activator function. Nat Cell Biol 6:626\u2013633. https:\/\/doi.org\/10.1038\/ncb1141","journal-title":"Nat Cell Biol"},{"key":"3774_CR54","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1016\/s0960-9822(03)00240-9","volume":"13","author":"MT Veeman","year":"2003","unstructured":"Veeman MT, Slusarski DC, Kaykas A, Louie SH, Moon RT (2003) Zebrafish prickle, a modulator of noncanonical Wnt\/Fz signaling, regulates gastrulation movements. Curr Biol 13:680\u2013685. https:\/\/doi.org\/10.1016\/s0960-9822(03)00240-9","journal-title":"Curr Biol"},{"key":"3774_CR55","doi-asserted-by":"publisher","first-page":"e139","DOI":"10.1161\/cir.0000000000000757","volume":"141","author":"SS Virani","year":"2020","unstructured":"Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Chang AR, Cheng S, Delling FN, Djousse L, Elkind MSV, Ferguson JF, Fornage M, Khan SS, Kissela BM, Knutson KL, Kwan TW, Lackland DT, Lewis TT, Lichtman JH, Longenecker CT, Loop MS, Lutsey PL, Martin SS, Matsushita K, Moran AE, Mussolino ME, Perak AM, Rosamond WD, Roth GA, Sampson UKA, Satou GM, Schroeder EB, Shah SH, Shay CM, Spartano NL, Stokes A, Tirschwell DL, VanWagner LB, Tsao CW (2020) Heart disease and stroke statistics\u20142020 update: a report from the American Heart Association. Circulation 141:e139\u2013e596. https:\/\/doi.org\/10.1161\/cir.0000000000000757","journal-title":"Circulation"},{"key":"3774_CR56","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1016\/j.athoracsur.2006.10.066","volume":"83","author":"KH Wu","year":"2007","unstructured":"Wu KH, Zhou B, Yu CT, Cui B, Lu SH, Han ZC, Liu YL (2007) Therapeutic potential of human umbilical cord derived stem cells in a rat myocardial infarction model. Ann Thorac Surg 83:1491\u20131498. https:\/\/doi.org\/10.1016\/j.athoracsur.2006.10.066","journal-title":"Ann Thorac Surg"},{"key":"3774_CR57","doi-asserted-by":"publisher","first-page":"318","DOI":"10.2174\/1566524019666191017150416","volume":"20","author":"L Yang","year":"2020","unstructured":"Yang L, Zhu S, Li Y, Zhuang J, Chen J, Huang H, Chen Y, Wen Y, Wen Y, Guo H, Fan X, Yuan W, Jiang Z, Wang Y, Wu X, Zhu P (2020) Overexpression of Pygo2 increases differentiation of human umbilical cord mesenchymal stem cells into cardiomyocyte-like cells. Curr Mol Med 20:318\u2013324. https:\/\/doi.org\/10.2174\/1566524019666191017150416","journal-title":"Curr Mol Med"},{"key":"3774_CR58","doi-asserted-by":"publisher","first-page":"3515","DOI":"10.3892\/mmr.2017.6454","volume":"15","author":"C Zhang","year":"2017","unstructured":"Zhang C, Zhou G, Cai C, Li J, Chen F, Xie L, Wang W, Zhang Y, Lai X, Ma L (2017) Human umbilical cord mesenchymal stem cells alleviate acute myocarditis by modulating endoplasmic reticulum stress and extracellular signal regulated 1\/2-mediated apoptosis. Mol Med Rep 15:3515\u20133520. https:\/\/doi.org\/10.3892\/mmr.2017.6454","journal-title":"Mol Med Rep"},{"key":"3774_CR59","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1097\/MCA.0b013e3283640f00","volume":"24","author":"W Zhang","year":"2013","unstructured":"Zhang W, Liu XC, Yang L, Zhu DL, Zhang YD, Chen Y, Zhang HY (2013) Wharton\u2019s jelly-derived mesenchymal stem cells promote myocardial regeneration and cardiac repair after miniswine acute myocardial infarction. Coron Artery Dis 24:549\u2013558. https:\/\/doi.org\/10.1097\/MCA.0b013e3283640f00","journal-title":"Coron Artery Dis"}],"container-title":["Cell and Tissue Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00441-023-03774-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00441-023-03774-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00441-023-03774-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T01:05:15Z","timestamp":1688173515000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00441-023-03774-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,26]]},"references-count":59,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["3774"],"URL":"https:\/\/doi.org\/10.1007\/s00441-023-03774-6","relation":{},"ISSN":["0302-766X","1432-0878"],"issn-type":[{"value":"0302-766X","type":"print"},{"value":"1432-0878","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,26]]},"assertion":[{"value":"30 August 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 April 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 May 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The hUC-MSCs were isolated from umbilical cords, which were obtained from healthy infants delivered by caesarean section at the Third Xiangya Hospital of Central South University in December 2019 and the Ethics Committee of this hospital approved this study (no. 20042). This study was approved by the Ethics Review Board of the Guangdong Provincial People\u2019s Hospital (KY-Z-2021\u2013609-01).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Informed consent was obtained from the mother who offered the umbilical cords.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}