{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Xie Y"],"funding":["American Heart Association-American Stroke Association","NIEHS NIH HHS","NHLBI NIH HHS","NIMH NIH HHS","NCI NIH HHS","NIH HHS"],"pagination":["1060-1077"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10959502"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["2(11)"],"pubmed_abstract":["Direct reprogramming of fibroblasts into induced cardiomyocytes holds great promise for heart regeneration. Although considerable progress has been made in understanding the transcriptional and epigenetic mechanisms of iCM reprogramming, its translational regulation remains largely unexplored. Here, we characterized the translational landscape of iCM reprogramming through integrative ribosome and transcriptomic profiling, and found extensive translatome repatterning during this process. Loss of function screening for translational regulators uncovered Ybx1 as a critical barrier to iCM induction. In a mouse model of myocardial infarction, removing <i>Ybx1</i> enhanced in vivo reprogramming, resulting in improved heart function and reduced scar size. Mechanistically, <i>Ybx1</i> depletion de-repressed the translation of its direct targets <i>SRF</i> and <i>Baf60c</i>, both of which mediated the effect of <i>Ybx1</i> depletion on iCM generation. Furthermore, removal of Ybx1 allowed single factor Tbx5-mediated iCM conversion. In summary, this study revealed a new layer of regulatory mechanism that controls cardiac reprogramming at the translational level."],"journal":["Nature cardiovascular research"],"pubmed_title":["Translational landscape of direct cardiac reprogramming reveals a role of Ybx1 in repressing cardiac fate acquisition."],"pmcid":["PMC10959502"],"funding_grant_id":["R01 HL139880","P30 CA016086","R01 HL139976","P30 ES010126","R01 HL164933","S10 OD026796","S10 MH124745","18TPA34180058","R35 HL155656"],"pubmed_authors":["Wang TW","Liu J","Xie Y","Lee SH","Shih YI","Wang H","Slattery C","Yang Y","Wang Q","Nguyen C","Farber G","Near D","Qian L","Colon M","Keepers B"],"additional_accession":[]},"is_claimable":false,"name":"Translational landscape of direct cardiac reprogramming reveals a role of Ybx1 in repressing cardiac fate acquisition.","description":"Direct reprogramming of fibroblasts into induced cardiomyocytes holds great promise for heart regeneration. Although considerable progress has been made in understanding the transcriptional and epigenetic mechanisms of iCM reprogramming, its translational regulation remains largely unexplored. Here, we characterized the translational landscape of iCM reprogramming through integrative ribosome and transcriptomic profiling, and found extensive translatome repatterning during this process. Loss of function screening for translational regulators uncovered Ybx1 as a critical barrier to iCM induction. In a mouse model of myocardial infarction, removing <i>Ybx1</i> enhanced in vivo reprogramming, resulting in improved heart function and reduced scar size. Mechanistically, <i>Ybx1</i> depletion de-repressed the translation of its direct targets <i>SRF</i> and <i>Baf60c</i>, both of which mediated the effect of <i>Ybx1</i> depletion on iCM generation. Furthermore, removal of Ybx1 allowed single factor Tbx5-mediated iCM conversion. In summary, this study revealed a new layer of regulatory mechanism that controls cardiac reprogramming at the translational level.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Nov","modification":"2026-05-28T03:18:37.539Z","creation":"2025-04-04T22:47:32.811Z"},"accession":"S-EPMC10959502","cross_references":{"pubmed":["38524149"],"doi":["10.1038/s44161-023-00344-5"]}}