• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

重编程衍生的基因组合可增加心肌细胞增殖以促进心脏再生。

Reprogramming-derived gene cocktail increases cardiomyocyte proliferation for heart regeneration.

作者信息

Cheng Yuan-Yuan, Yan Yu-Ting, Lundy David J, Lo Annie Ha, Wang Yu-Ping, Ruan Shu-Chian, Lin Po-Ju, Hsieh Patrick Ch

机构信息

Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

出版信息

EMBO Mol Med. 2017 Feb;9(2):251-264. doi: 10.15252/emmm.201606558.

DOI:10.15252/emmm.201606558
PMID:28011860
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5286362/
Abstract

Although remnant cardiomyocytes (CMs) possess a certain degree of proliferative ability, efficiency is too low for cardiac regeneration after injury. In this study, we identified a distinct stage within the initiation phase of CM reprogramming before the MET process, and microarray analysis revealed the strong up-regulation of several mitosis-related genes at this stage of reprogramming. Several candidate genes were selected and tested for their ability to induce CM proliferation. Delivering a cocktail of three genes, FoxM1, Id1, and Jnk3-shRNA (FIJs), induced CMs to re-enter the cell cycle and complete mitosis and cytokinesis in vitro More importantly, this gene cocktail increased CM proliferation in vivo and significantly improved cardiac function and reduced fibrosis after myocardial infarction. Collectively, our findings present a cocktail FIJs that may be useful in cardiac regeneration and also provide a practical strategy for probing reprogramming assays for regeneration of other tissues.

摘要

尽管残留的心肌细胞（CMs）具有一定程度的增殖能力，但对于损伤后的心脏再生而言，其效率过低。在本研究中，我们在中胚层到内胚层转变（MET）过程之前的CM重编程起始阶段确定了一个独特阶段，并且微阵列分析显示在该重编程阶段几个有丝分裂相关基因强烈上调。选择了几个候选基因并测试它们诱导CM增殖的能力。递送由三个基因FoxM1、Id1和Jnk3-shRNA（FIJs）组成的混合物，可诱导CM在体外重新进入细胞周期并完成有丝分裂和胞质分裂。更重要的是，这种基因混合物在体内增加了CM增殖，并显著改善了心肌梗死后的心脏功能并减少了纤维化。总体而言，我们的研究结果提出了一种可能对心脏再生有用的FIJs混合物，并且还为探索用于其他组织再生的重编程分析提供了一种实用策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b51/5286362/f9582f8c76d8/EMMM-9-251-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b51/5286362/587c765c80f3/EMMM-9-251-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b51/5286362/7d1794c774a1/EMMM-9-251-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b51/5286362/c25d3bf27b9e/EMMM-9-251-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b51/5286362/5bc652ae8918/EMMM-9-251-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b51/5286362/774eb6dd1aa6/EMMM-9-251-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b51/5286362/f9582f8c76d8/EMMM-9-251-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b51/5286362/587c765c80f3/EMMM-9-251-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b51/5286362/7d1794c774a1/EMMM-9-251-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b51/5286362/c25d3bf27b9e/EMMM-9-251-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b51/5286362/5bc652ae8918/EMMM-9-251-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b51/5286362/774eb6dd1aa6/EMMM-9-251-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b51/5286362/f9582f8c76d8/EMMM-9-251-g007.jpg

相似文献

1
Reprogramming-derived gene cocktail increases cardiomyocyte proliferation for heart regeneration.重编程衍生的基因组合可增加心肌细胞增殖以促进心脏再生。
EMBO Mol Med. 2017 Feb;9(2):251-264. doi: 10.15252/emmm.201606558.
2
Direct reprogramming induces vascular regeneration post muscle ischemic injury.直接重编程诱导肌肉缺血损伤后的血管再生。
Mol Ther. 2021 Oct 6;29(10):3042-3058. doi: 10.1016/j.ymthe.2021.07.014. Epub 2021 Jul 29.
3
Improved Cardiac Function in Postischemic Rats Using an Optimized Cardiac Reprogramming Cocktail Delivered in a Single Novel Adeno-Associated Virus.优化的心脏重编程鸡尾酒单次经新型腺相关病毒载体传递改善缺血后大鼠心功能。
Circulation. 2023 Oct 3;148(14):1099-1112. doi: 10.1161/CIRCULATIONAHA.122.061542. Epub 2023 Aug 21.
4
Foxm1 regulates cardiomyocyte proliferation in adult zebrafish after cardiac injury.Foxm1 调控成年斑马鱼心脏损伤后的心肌细胞增殖。
Development. 2023 Mar 15;150(6). doi: 10.1242/dev.201163. Epub 2023 Mar 14.
5
Therapeutic role of miR-19a/19b in cardiac regeneration and protection from myocardial infarction.miR-19a/19b 在心脏再生和心肌梗保护中的治疗作用。
Nat Commun. 2019 Apr 17;10(1):1802. doi: 10.1038/s41467-019-09530-1.
6
ALKBH5 regulates cardiomyocyte proliferation and heart regeneration by demethylating the mRNA of YTHDF1.ALKBH5 通过去甲基化 YTHDF1 的 mRNA 来调节心肌细胞增殖和心脏再生。
Theranostics. 2021 Jan 1;11(6):3000-3016. doi: 10.7150/thno.47354. eCollection 2021.
7
Long Noncoding RNA CPR (Cardiomyocyte Proliferation Regulator) Regulates Cardiomyocyte Proliferation and Cardiac Repair.长链非编码 RNA CPR（心肌细胞增殖调节剂）调节心肌细胞增殖和心脏修复。
Circulation. 2019 Jun 4;139(23):2668-2684. doi: 10.1161/CIRCULATIONAHA.118.035832. Epub 2019 Mar 5.
8
The Long Noncoding RNA CAREL Controls Cardiac Regeneration.长非编码 RNA CAREL 控制心脏再生。
J Am Coll Cardiol. 2018 Jul 31;72(5):534-550. doi: 10.1016/j.jacc.2018.04.085. Epub 2018 Jul 2.
9
Cardiac regeneration: the gene therapy approach.心脏再生：基因治疗方法。
Expert Opin Biol Ther. 2009 Apr;9(4):411-25. doi: 10.1517/14712590902806364.
10
IL-13 promotes in vivo neonatal cardiomyocyte cell cycle activity and heart regeneration.IL-13 促进体内新生大鼠心肌细胞的细胞周期活性和心脏再生。
Am J Physiol Heart Circ Physiol. 2019 Jan 1;316(1):H24-H34. doi: 10.1152/ajpheart.00521.2018. Epub 2018 Oct 19.

引用本文的文献

1
Matured hiPSC-derived cardiomyocytes possess dematuration plasticity.成熟的人诱导多能干细胞衍生的心肌细胞具有去分化可塑性。
J Mol Cell Cardiol Plus. 2025 Mar 28;12:100295. doi: 10.1016/j.jmccpl.2025.100295. eCollection 2025 Jun.
2
Direct fibroblast reprogramming: an emerging strategy for treating organic fibrosis.直接成纤维细胞重编程：一种治疗器官纤维化的新兴策略。
J Transl Med. 2025 Feb 27;23(1):240. doi: 10.1186/s12967-024-06060-3.
3
The role of JNK signaling pathway in organ fibrosis.JNK信号通路在器官纤维化中的作用。

本文引用的文献

1
Conversion of human fibroblasts into functional cardiomyocytes by small molecules.小分子将人成纤维细胞转化为功能性心肌细胞。
Science. 2016 Jun 3;352(6290):1216-20. doi: 10.1126/science.aaf1502. Epub 2016 Apr 28.
2
Human iPS cell-engineered cardiac tissue sheets with cardiomyocytes and vascular cells for cardiac regeneration.用于心脏再生的含心肌细胞和血管细胞的人诱导多能干细胞工程化心脏组织片。
Sci Rep. 2014 Oct 22;4:6716. doi: 10.1038/srep06716.
3
A proliferative burst during preadolescence establishes the final cardiomyocyte number.
J Adv Res. 2025 Aug;74:207-223. doi: 10.1016/j.jare.2024.09.029. Epub 2024 Oct 2.
4
Potential Application of Modified mRNA in Cardiac Regeneration.修饰信使 RNA 在心脏再生中的潜在应用。
Cell Transplant. 2024 Jan-Dec;33:9636897241248956. doi: 10.1177/09636897241248956.
5
Cardiac regeneration: Pre-existing cardiomyocyte as the hub of novel signaling pathway.心脏再生：现存心肌细胞作为新信号通路的核心
Genes Dis. 2023 Mar 24;11(2):747-759. doi: 10.1016/j.gendis.2023.01.031. eCollection 2024 Mar.
6
Foxm1 regulates cardiomyocyte proliferation in adult zebrafish after cardiac injury.Foxm1 调控成年斑马鱼心脏损伤后的心肌细胞增殖。
Development. 2023 Mar 15;150(6). doi: 10.1242/dev.201163. Epub 2023 Mar 14.
7
Metabolic Changes Associated With Cardiomyocyte Dedifferentiation Enable Adult Mammalian Cardiac Regeneration.与心肌细胞去分化相关的代谢变化使成年哺乳动物的心脏再生成为可能。
Circulation. 2022 Dec 20;146(25):1950-1967. doi: 10.1161/CIRCULATIONAHA.122.061960. Epub 2022 Nov 24.
8
Cardiac Remodeling and Repair: Recent Approaches, Advancements, and Future Perspective.心脏重构与修复：近期方法、进展及未来展望。
Int J Mol Sci. 2021 Dec 3;22(23):13104. doi: 10.3390/ijms222313104.
9
BMP and Notch Signaling Pathways differentially regulate Cardiomyocyte Proliferation during Ventricle Regeneration.BMP 和 Notch 信号通路在心室再生过程中差异调节心肌细胞增殖。
Int J Biol Sci. 2021 May 27;17(9):2157-2166. doi: 10.7150/ijbs.59648. eCollection 2021.
10
Transient reprogramming of postnatal cardiomyocytes to a dedifferentiated state.将出生后心肌细胞瞬时重编程为去分化状态。
PLoS One. 2021 May 5;16(5):e0251054. doi: 10.1371/journal.pone.0251054. eCollection 2021.
青春期前的增殖爆发确立了心肌细胞的最终数量。
Cell. 2014 May 8;157(4):795-807. doi: 10.1016/j.cell.2014.03.035.
4
Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts.人类胚胎干细胞衍生的心肌细胞可使非人类灵长类动物的心脏再生。
Nature. 2014 Jun 12;510(7504):273-7. doi: 10.1038/nature13233. Epub 2014 Apr 30.
5
Cyclin A2 induces cardiac regeneration after myocardial infarction through cytokinesis of adult cardiomyocytes.周期蛋白 A2 通过成年心肌细胞的胞质分裂诱导心肌梗死后的心脏再生。
Sci Transl Med. 2014 Feb 19;6(224):224ra27. doi: 10.1126/scitranslmed.3007668.
6
WT1 regulates the expression of inhibitory chemokines during heart development.WT1 在心脏发育过程中调节抑制性趋化因子的表达。
Hum Mol Genet. 2013 Dec 20;22(25):5083-95. doi: 10.1093/hmg/ddt358. Epub 2013 Jul 29.
7
In vivo cardiac reprogramming contributes to zebrafish heart regeneration.体内心脏重编程有助于斑马鱼心脏再生。
Nature. 2013 Jun 27;498(7455):497-501. doi: 10.1038/nature12322. Epub 2013 Jun 19.
8
Meis1 regulates postnatal cardiomyocyte cell cycle arrest.Meis1 调控心肌细胞出生后的细胞周期停滞。
Nature. 2013 May 9;497(7448):249-253. doi: 10.1038/nature12054. Epub 2013 Apr 17.
9
Highly coordinated proteome dynamics during reprogramming of somatic cells to pluripotency.体细胞重编程为多能性过程中高度协调的蛋白质组动力学。
Cell Rep. 2012 Dec 27;2(6):1579-92. doi: 10.1016/j.celrep.2012.10.014.
10
A molecular roadmap of reprogramming somatic cells into iPS cells.重编程体细胞为诱导多能干细胞的分子路线图。
Cell. 2012 Dec 21;151(7):1617-32. doi: 10.1016/j.cell.2012.11.039.