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DOI | 10.1038/s41586-020-2228-6 |
A calcineurin-Hoxb13 axis regulates growth mode of mammalian cardiomyocytes | |
Waszak, Sebastian M.1; Robinson, Giles W.2; Gudenas, Brian L.3; Smith, Kyle S.3; Forget, Antoine4; Kojic, Marija5; Garcia-Lopez, Jesus3; Hadley, Jennifer3; Hamilton, Kayla V.6; Indersie, Emilie4; Buchhalter, Ivo7; Kerssemakers, Jules7; Jaeger, Natalie8,9; Sharma, Tanvi8,9; Rausch, Tobias1 | |
2020-04-01 | |
发表期刊 | NATURE |
ISSN | 0028-0836 |
EISSN | 1476-4687 |
出版年 | 2020 |
卷号 | 582期号:7811页码:271-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Singapore; Peoples R China |
英文关键词 | Hoxb13 acts as a cofactor of Meis1 in regulating cardiomyocyte maturation and cell cycle, and knockout of both proteins enables regeneration of postnatal cardiac tissue in a mouse model of heart injury. A major factor in the progression to heart failure in humans is the inability of the adult heart to repair itself after injury. We recently demonstrated that the early postnatal mammalian heart is capable of regeneration following injury through proliferation of preexisting cardiomyocytes(1,2) and that Meis1, a three amino acid loop extension (TALE) family homeodomain transcription factor, translocates to cardiomyocyte nuclei shortly after birth and mediates postnatal cell cycle arrest(3). Here we report that Hoxb13 acts as a cofactor of Meis1 in postnatal cardiomyocytes. Cardiomyocyte-specific deletion of Hoxb13 can extend the postnatal window of cardiomyocyte proliferation and reactivate the cardiomyocyte cell cycle in the adult heart. Moreover, adult Meis1-Hoxb13 double-knockout hearts display widespread cardiomyocyte mitosis, sarcomere disassembly and improved left ventricular systolic function following myocardial infarction, as demonstrated by echocardiography and magnetic resonance imaging. Chromatin immunoprecipitation with sequencing demonstrates that Meis1 and Hoxb13 act cooperatively to regulate cardiomyocyte maturation and cell cycle. Finally, we show that the calcium-activated protein phosphatase calcineurin dephosphorylates Hoxb13 at serine-204, resulting in its nuclear localization and cell cycle arrest. These results demonstrate that Meis1 and Hoxb13 act cooperatively to regulate cardiomyocyte maturation and proliferation and provide mechanistic insights into the link between hyperplastic and hypertrophic growth of cardiomyocytes. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000528161900004 |
WOS关键词 | CARDIAC-HYPERTROPHY ; HEART REGENERATION ; DNA-SYNTHESIS ; CALCIUM ; MEIS1 ; PROLIFERATION ; PROTEINS ; RENEWAL ; PATHWAY ; BINDING |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/281536 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.European Mol Biol Lab, Genome Biol Unit, Heidelberg, Germany; 2.St Jude Childrens Res Hosp, Dept Oncol, Div Neurooncol, 332 N Lauderdale St, Memphis, TN 38105 USA; 3.St Jude Childrens Res Hosp, Dept Dev Neurobiol, 332 N Lauderdale St, Memphis, TN 38105 USA; 4.Univ Paris Saclay, Univ Paris Sud, CNRS, INSERM,UMR 3347,U1021, Orsay, France; 5.Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia; 6.St Jude Childrens Res Hosp, Dept Oncol, Div Canc Predisposit, 332 N Lauderdale St, Memphis, TN 38105 USA; 7.German Canc Res Ctr, Omics IT & Data Management Core Facil W610, Heidelberg, Germany; 8.Hopp Childrens Canc Ctr Heidelberg KiTZ, Heidelberg, Germany; 9.German Canc Res Ctr, German Consortium Translat Canc Res DKTK, Div Pediat Neurooncol, Heidelberg, Germany; 10.Princess Maxima Ctr Pediat Oncol, Utrecht, Netherlands; 11.German Canc Res Ctr, Pediat Glioma Res Grp, Heidelberg, Germany; 12.St Jude Childrens Res Hosp, Canc Ctr Adm, 332 N Lauderdale St, Memphis, TN 38105 USA; 13.St Jude Childrens Res Hosp, Dept Pathol, 332 N Lauderdale St, Memphis, TN 38105 USA; 14.St Jude Childrens Res Hosp, Hartwell Ctr, 332 N Lauderdale St, Memphis, TN 38105 USA; 15.PSL Res Univ, Inst Curie, Ctr Rech, Lab Spectrometrie Masse Prote, Paris, France; 16.St Jude Childrens Res Hosp, Dept Computat Biol, 332 N Lauderdale St, Memphis, TN 38105 USA; 17.Univ Texas Southwestern Med Sch, Div Pediat Hematol Oncol, Dallas, TX USA; 18.Childrens Hosp & Clin Minnesota, Dept Pediat Hematol & Oncol, Minneapolis, MN USA; 19.Stanford Univ, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA; 20.Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA; 21.Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA; 22.Rady Childrens Hosp, San Diego, CA USA; 23.Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA; 24.Perth Childrens Hosp, Dept Paediat & Adolescent Oncol Haematol, Perth, WA, Australia; 25.Telethon Kids Inst, Brain Tumour Res Programme, Perth, WA, Australia; 26.Arnold Palmer Hosp Ctr Childrens Canc, Orlando, FL USA; 27.Univ Paris Saclay, Dept Pediat & Adolescent Oncol, Villejuif, France; 28.Univ Med Ctr Hamburg Eppendorf, Dept Pediat Hematol & Oncol, Hamburg, Germany; 29.Canc Registry Norway, Oslo, Norway; 30.Canc Registry Norway, Inst Populat Based Canc Res, Dept Res, Oslo, Norway; 31.Karolinska Inst, Inst Environm Med, Stockholm, Sweden; 32.Univ Gothenburg, Queen Silvia Childrens Hosp, Dept Pediat, Gothenburg, Sweden; 33.Int Agcy Res Canc, Sect Environm & Radiat, Lyon, France; 34.Univ Copenhagen, Rigshosp, Finsen Ctr, Oncol Clin, Copenhagen, Denmark; 35.Danish Canc Soc, Res Ctr, Copenhagen, Denmark; 36.Univ Basel, Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland; 37.Univ Bern, Inst Social & Prevent Med, Swiss Childhood Canc Registry, Bern, Switzerland; 38.Univ Childrens Hosp, Dept Paediat Haematol & Oncol, Bern, Switzerland; 39.Univ Childrens Hosp Zurich, Zurich, Switzerland; 40.Univ Hosp Dusseldorf, Dept Pediat Oncol Hematol & Clin Immunol, Fac Med, Dusseldorf, Germany; 41.Univ Paris, Necker Hosp, Dept Pediat Neurosurg, Paris, France; 42.Heidelberg Univ Hosp, Dept Pediat Hematol & Oncol, Heidelberg, Germany; 43.German Canc Res Ctr, Clin Cooperat Unit Pediat Oncol, Heidelberg, Germany; 44.Burdenko Neurosurg Inst, Dept Neuropathol, Moscow, Russia; 45.German Canc Res Ctr, Clin Cooperat Unit Neuropathol, Heidelberg, Germany; 46.Univ Hosp, Dept Neuropathol, Heidelberg, Germany; 47.German Canc Res Ctr Heidelberg DKFZ, German Consortium Translat Canc Res DKTK, Div Mol Genet, Heidelberg, Germany |
推荐引用方式 GB/T 7714 | Waszak, Sebastian M.,Robinson, Giles W.,Gudenas, Brian L.,et al. A calcineurin-Hoxb13 axis regulates growth mode of mammalian cardiomyocytes[J]. NATURE,2020,582(7811):271-+. |
APA | Waszak, Sebastian M..,Robinson, Giles W..,Gudenas, Brian L..,Smith, Kyle S..,Forget, Antoine.,...&Rausch, Tobias.(2020).A calcineurin-Hoxb13 axis regulates growth mode of mammalian cardiomyocytes.NATURE,582(7811),271-+. |
MLA | Waszak, Sebastian M.,et al."A calcineurin-Hoxb13 axis regulates growth mode of mammalian cardiomyocytes".NATURE 582.7811(2020):271-+. |
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