{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T11:36:55Z","timestamp":1786534615620,"version":"build-2736575974"},"reference-count":79,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LZ19H040001"],"award-info":[{"award-number":["LZ19H040001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Left ventricular noncompaction (LVNC) is a cardiomyopathy characterized by excessive trabeculation and deep intertrabecular recesses, yet its molecular mechanisms remain poorly understood. Here, we identify Bcl11b as a novel regulator of cardiomyocyte (CM) growth and ventricular wall maturation. CM-specific deletion of Bcl11b in mice recapitulates key LVNC features, including increased noncompacted-to-compacted ratio, impaired compact layer expansion, reduced CM proliferation and size, and systolic dysfunction. Mechanistically, Bcl11b deficiency leads to marked upregulation of Pou3f2, a transcriptional repressor that further suppresses Titin (TTN) expression. Loss of Bcl11b disrupts sarcomere integrity and reduces TTN protein levels, while forced Pou3f2 overexpression similarly represses TTN. Notably, heterozygous loss of Pou3f2 rescues the LVNC phenotype in Bcl11b-deficient hearts, restoring CM growth and TTN expression. Our findings identify a critical relationship among Bcl11b, Pou3f2 and TTN that controls CM proliferation and hypertrophic maturation during cardiac development. Dysregulation of this regulatory network impairs ventricular compaction and contributes to the pathogenesis of LVNC, providing new mechanistic insights into disease pathogenesis and highlighting potential therapeutic targets.<\/jats:p>","DOI":"10.3390\/ijms27167199","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T11:02:11Z","timestamp":1786532531000},"page":"7199","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cardiomyocyte-Specific bcl11b Knockout Causes Left Ventricular Noncompaction by Dysregulating pou3f2 and Titin"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3610-1394","authenticated-orcid":false,"given":"Wei","family":"Bi","sequence":"first","affiliation":[{"name":"School of Life Science, Fudan University, Shanghai 200433, China"},{"name":"Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310030, China"},{"name":"Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310030, China"},{"name":"Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou 310030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8420-8672","authenticated-orcid":false,"given":"Xiaoxi","family":"Luo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310030, China"},{"name":"Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310030, China"},{"name":"Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou 310030, China"},{"name":"Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9247-699X","authenticated-orcid":false,"given":"Yaqi","family":"Lv","sequence":"additional","affiliation":[{"name":"Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310030, China"},{"name":"Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310030, China"},{"name":"Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou 310030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310030, China"},{"name":"Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310030, China"},{"name":"Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou 310030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youshi","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310030, China"},{"name":"Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310030, China"},{"name":"Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou 310030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxi","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310030, China"},{"name":"Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310030, China"},{"name":"Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou 310030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiani","family":"Fu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310030, China"},{"name":"Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310030, China"},{"name":"Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou 310030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijia","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310030, China"},{"name":"Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310030, China"},{"name":"Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou 310030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310030, China"},{"name":"Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310030, China"},{"name":"Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou 310030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Chang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310030, China"},{"name":"Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310030, China"},{"name":"Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou 310030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjun","family":"Shi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310030, China"},{"name":"Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310030, China"},{"name":"Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou 310030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1161\/01.CIR.82.2.507","article-title":"Isolated noncompaction of left ventricular myocardium. 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