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However, the regulatory mechanism of lncRNAs in early heart development is still limited. In this study, we identified cardiac mesoderm-related lncRNA (LncCMRR). Knockout (KO) of LncCMRR decreased the formation potential of cardiac mesoderm and cardiomyocytes during embryoid body differentiation of mouse embryonic stem (ES) cells. Mechanistic analyses showed that LncCMRR functionally interacted with the transcription suppressor PURB and inhibited its binding potential at the promoter region of Flk1, which safeguarded the transcription of Flk1 during cardiac mesoderm formation. We also carried out gene ontology term and signaling pathway enrichment analyses for the differentially expressed genes after KO of LncCMRR, and found significant correlation of LncCMRR with cardiac muscle contraction, dilated cardiomyopathy, and hypertrophic cardiomyopathy. Consistently, the expression level of Flk1 at E7.75 and the thickness of myocardium at E17.5 were significantly decreased after KO of LncCMRR, and the survival rate and heart function index of LncCMRR-KO mice were also significantly decreased as compared with the wild-type group. These findings indicated that the defects in early heart development led to functional abnormalities in adulthood heart of LncCMRR-KO mice. Conclusively, our findings elucidate the main function and regulatory mechanism of LncCMRR in cardiac mesoderm formation, and provide new insights into lncRNA-mediated regulatory network of mouse ES cell differentiation.<\/jats:p>","DOI":"10.1093\/stmcls\/sxac077","type":"journal-article","created":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T14:55:01Z","timestamp":1667228101000},"page":"11-25","source":"Crossref","is-referenced-by-count":4,"title":["LncCMRR Plays an Important Role in Cardiac Differentiation by Regulating the Purb\/Flk1 Axis"],"prefix":"10.1093","volume":"41","author":[{"given":"Yiwei","family":"Yang","sequence":"first","affiliation":[{"name":"Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, National Stem Cell Translational Resource Center, School of Life Sciences and Technology, Tongji University , Shanghai , 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Tongji University , Shanghai , People\u2019s Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenqi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Computational Biology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University , Shanghai , People\u2019s Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7538-1889","authenticated-orcid":false,"given":"Jiuhong","family":"Kang","sequence":"additional","affiliation":[{"name":"Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, National Stem Cell Translational Resource Center, School of Life Sciences and Technology, Tongji University , Shanghai , People\u2019s Republic of 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