{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T21:06:11Z","timestamp":1790197571614,"version":"4.1.0"},"reference-count":39,"publisher":"The Company of Biologists","issue":"18","license":[{"start":{"date-parts":[[2019,3,15]],"date-time":"2019-03-15T00:00:00Z","timestamp":1552608000000},"content-version":"vor","delay-in-days":181,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/100007915","name":"Baylor College of Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007915","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["1S10OD016167"],"award-info":[{"award-number":["1S10OD016167"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["U54 HD083092"],"award-info":[{"award-number":["U54 HD083092"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fondation Leducq Transatlantic Networks of Excellence in Cardiovascular Research","award":["14CVD01"],"award-info":[{"award-number":["14CVD01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,9,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Loss of the paired-like homeodomain transcription factor 2 (Pitx2) in cardiomyocytes predisposes mice to atrial fibrillation and compromises neonatal regenerative capacity. In addition, Pitx2 gain-of-function protects mature cardiomyocytes from ischemic injury and promotes heart repair. Here, we characterized the long-term myocardial phenotype following myocardial infarction (MI) in Pitx2 conditional-knockout (Pitx2 CKO) mice. We found adipose-like tissue in Pitx2 CKO hearts 60\u2005days after MI induced surgically at postnatal day 2 but not at day 8. Molecular and cellular analyses showed the onset of adipogenic signaling in mutant hearts after MI. Lineage tracing experiments showed a non-cardiomyocyte origin of the de novo adipose-like tissue. Interestingly, we found that Pitx2 promotes mitochondrial function through its gene regulatory network, and that the knockdown of a key mitochondrial Pitx2 target gene, Cox7c, also leads to the accumulation of myocardial fat tissue. Single-nuclei RNA-seq revealed that Pitx2-deficient hearts were oxidatively stressed. Our findings reveal a role for Pitx2 in maintaining proper cardiac cellular composition during heart regeneration via the maintenance of proper mitochondrial structure and function.<\/jats:p>","DOI":"10.1242\/dev.168609","type":"journal-article","created":{"date-parts":[[2018,8,24]],"date-time":"2018-08-24T14:55:11Z","timestamp":1535122511000},"source":"Crossref","is-referenced-by-count":42,"title":["<i>Pitx2<\/i> maintains mitochondrial function during regeneration to prevent myocardial fat deposition"],"prefix":"10.1242","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3607-3821","authenticated-orcid":false,"given":"Lele","family":"Li","sequence":"first","affiliation":[{"name":"Baylor College of Medicine 1 Department of Molecular Physiology and Biophysics , , Houston, TX 77030 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Tao","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine 1 Department of Molecular Physiology and Biophysics , , Houston, TX 77030 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew C.","family":"Hill","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine 2 Program in Developmental Biology , , Houston, TX 77030 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7055-6790","authenticated-orcid":false,"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Children's Medical Center 3 , , 200127 Shanghai , China"},{"name":"Shanghai Jiao Tong University School of Medicine 3 , , 200127 Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Morikawa","sequence":"additional","affiliation":[{"name":"Cardiomyocyte Renewal Laboratory 4 , , Houston, TX 77030 , USA"},{"name":"Texas Heart Institute 4 , , Houston, TX 77030 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7842-9857","authenticated-orcid":false,"given":"James F.","family":"Martin","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine 1 Department of Molecular Physiology and Biophysics , , Houston, TX 77030 , USA"},{"name":"Baylor College of Medicine 2 Program in Developmental Biology , , Houston, TX 77030 , USA"},{"name":"Cardiomyocyte Renewal Laboratory 4 , , Houston, TX 77030 , USA"},{"name":"Texas Heart Institute 4 , , Houston, TX 77030 , USA"},{"name":"Cardiovascular Research Institute, Baylor College of Medicine 5 , Houston, TX 77030 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2018,9,26]]},"reference":[{"key":"2024061300162555900_DEV168609C1","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1016\/j.scr.2016.04.011","article-title":"Genome-wide analysis of gene expression during adipogenesis in human adipose-derived stromal cells reveals novel patterns of gene expression during adipocyte differentiation","volume":"16","author":"Ambele","year":"2016","journal-title":"Stem Cell Res."},{"key":"2024061300162555900_DEV168609C2","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1182\/blood-2012-06-437988","article-title":"Connective tissue growth factor regulates adipocyte differentiation of mesenchymal stromal cells and facilitates leukemia bone marrow engraftment","volume":"122","author":"Battula","year":"2013","journal-title":"Blood"},{"key":"2024061300162555900_DEV168609C3","doi-asserted-by":"publisher","first-page":"1566","DOI":"10.1016\/j.cell.2015.05.026","article-title":"Dynamics of cell generation and turnover in the human heart","volume":"161","author":"Bergmann","year":"2015","journal-title":"Cell"},{"key":"2024061300162555900_DEV168609C4","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1016\/S1097-2765(00)80155-0","article-title":"A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance","volume":"2","author":"Br\u00fcning","year":"1998","journal-title":"Mol. 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