• 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

再生增强元件对组织修复的调节作用。

Modulation of tissue repair by regeneration enhancer elements.

作者信息

Kang Junsu, Hu Jianxin, Karra Ravi, Dickson Amy L, Tornini Valerie A, Nachtrab Gregory, Gemberling Matthew, Goldman Joseph A, Black Brian L, Poss Kenneth D

机构信息

Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.

Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California 94143, USA.

出版信息

Nature. 2016 Apr 14;532(7598):201-6. doi: 10.1038/nature17644. Epub 2016 Apr 6.

DOI:10.1038/nature17644
PMID:27049946
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4844022/
Abstract

How tissue regeneration programs are triggered by injury has received limited research attention. Here we investigate the existence of enhancer regulatory elements that are activated in regenerating tissue. Transcriptomic analyses reveal that leptin b (lepb) is highly induced in regenerating hearts and fins of zebrafish. Epigenetic profiling identified a short DNA sequence element upstream and distal to lepb that acquires open chromatin marks during regeneration and enables injury-dependent expression from minimal promoters. This element could activate expression in injured neonatal mouse tissues and was divisible into tissue-specific modules sufficient for expression in regenerating zebrafish fins or hearts. Simple enhancer-effector transgenes employing lepb-linked sequences upstream of pro- or anti-regenerative factors controlled the efficacy of regeneration in zebrafish. Our findings provide evidence for 'tissue regeneration enhancer elements' (TREEs) that trigger gene expression in injury sites and can be engineered to modulate the regenerative potential of vertebrate organs.

摘要

组织再生程序如何由损伤触发，这方面的研究关注有限。在此，我们研究了在再生组织中被激活的增强子调控元件的存在情况。转录组分析表明，瘦素b（lepb）在斑马鱼再生的心脏和鳍中高度诱导表达。表观遗传分析确定了lepb上游和远端的一段短DNA序列元件，该元件在再生过程中获得开放染色质标记，并能使最小启动子实现损伤依赖性表达。该元件可在新生小鼠损伤组织中激活表达，并可分为足以在斑马鱼再生鳍或心脏中表达的组织特异性模块。采用促再生或抗再生因子上游与lepb相连序列的简单增强子-效应子转基因，可控制斑马鱼的再生效果。我们的研究结果为“组织再生增强子元件”（TREEs）提供了证据，这些元件在损伤部位触发基因表达，并且可以进行工程设计以调节脊椎动物器官的再生潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/90e83ffba045/nihms776933f16.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/49a167d4018c/nihms776933f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/6c2a80c6f121/nihms776933f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/dec669c7d6d6/nihms776933f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/5208b690d896/nihms776933f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/523f59a85ffc/nihms776933f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/b4f369cd749b/nihms776933f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/dbd3ba7cd612/nihms776933f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/fbe8382aabe8/nihms776933f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/03f0ca7ee3f3/nihms776933f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/2d1e2c6247ea/nihms776933f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/792de0b649d0/nihms776933f11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/8d20d02cf826/nihms776933f12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/4236cea87c33/nihms776933f13.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/b41358614dd3/nihms776933f14.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/6ffa94e08abe/nihms776933f15.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/90e83ffba045/nihms776933f16.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/49a167d4018c/nihms776933f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/6c2a80c6f121/nihms776933f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/dec669c7d6d6/nihms776933f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/5208b690d896/nihms776933f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/523f59a85ffc/nihms776933f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/b4f369cd749b/nihms776933f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/dbd3ba7cd612/nihms776933f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/fbe8382aabe8/nihms776933f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/03f0ca7ee3f3/nihms776933f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/2d1e2c6247ea/nihms776933f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/792de0b649d0/nihms776933f11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/8d20d02cf826/nihms776933f12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/4236cea87c33/nihms776933f13.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/b41358614dd3/nihms776933f14.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/6ffa94e08abe/nihms776933f15.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f446/4844022/90e83ffba045/nihms776933f16.jpg

相似文献

1
Modulation of tissue repair by regeneration enhancer elements.再生增强元件对组织修复的调节作用。
Nature. 2016 Apr 14;532(7598):201-6. doi: 10.1038/nature17644. Epub 2016 Apr 6.
2
Identification and requirements of enhancers that direct gene expression during zebrafish fin regeneration.鉴定和确定指导斑马鱼鳍再生过程中基因表达的增强子。
Development. 2020 Jul 30;147(14):dev191262. doi: 10.1242/dev.191262.
3
Resolving Heart Regeneration by Replacement Histone Profiling.通过置换组蛋白分析解决心脏再生问题。
Dev Cell. 2017 Feb 27;40(4):392-404.e5. doi: 10.1016/j.devcel.2017.01.013.
4
The careg element reveals a common regulation of regeneration in the zebrafish myocardium and fin.该 careg 元件揭示了斑马鱼心脏和鳍再生的共同调控机制。
Nat Commun. 2017 May 3;8:15151. doi: 10.1038/ncomms15151.
5
leptin b and its regeneration enhancer illustrate the regenerative features of zebrafish hearts.瘦素 b 及其再生增强因子说明了斑马鱼心脏的再生特征。
Dev Dyn. 2024 Jan;253(1):91-106. doi: 10.1002/dvdy.556. Epub 2022 Dec 16.
6
Differentiated skeletal cells contribute to blastema formation during zebrafish fin regeneration.分化的骨骼细胞有助于斑马鱼鳍再生过程中的芽基形成。
Development. 2011 Sep;138(18):3897-905. doi: 10.1242/dev.064717.
7
Identification of enhancer regulatory elements that direct epicardial gene expression during zebrafish heart regeneration.鉴定指导斑马鱼心脏再生过程中心外膜基因表达的增强子调控元件。
Development. 2022 Feb 15;149(4). doi: 10.1242/dev.200133. Epub 2022 Feb 18.
8
Decoding an organ regeneration switch by dissecting cardiac regeneration enhancers.通过剖析心脏再生增强子来解码器官再生开关。
Development. 2020 Dec 23;147(24):dev194019. doi: 10.1242/dev.194019.
9
A diffusible signal derived from hematopoietic cells supports the survival and proliferation of regenerative cells during zebrafish fin fold regeneration.源自造血细胞的一种可扩散信号在斑马鱼鳍褶再生过程中支持再生细胞的存活和增殖。
Dev Biol. 2015 Mar 1;399(1):80-90. doi: 10.1016/j.ydbio.2014.12.015. Epub 2014 Dec 19.
10
Dynamics of zebrafish fin regeneration using a pulsed SILAC approach.使用脉冲式稳定同位素标记氨基酸法（pulsed SILAC）研究斑马鱼鳍再生的动力学
Proteomics. 2015 Feb;15(4):739-51. doi: 10.1002/pmic.201400316.

引用本文的文献

1
MEF2C controls segment-specific gene regulatory networks that direct heart tube morphogenesis.MEF2C控制指导心脏管形态发生的节段特异性基因调控网络。
Genes Dev. 2025 Aug 29. doi: 10.1101/gad.352889.125.
2
PS77: a novel peptide with α-helical structure for targeted anti-inflammatory therapy in biomaterials design.PS77：一种具有α螺旋结构的新型肽，用于生物材料设计中的靶向抗炎治疗。
Immunol Res. 2025 Jul 24;73(1):110. doi: 10.1007/s12026-025-09663-0.
3
Spatial and longitudinal tracking of enhancer-AAV vectors that target transgene expression to injured mouse myocardium.

本文引用的文献

1
Evolving New Skeletal Traits by cis-Regulatory Changes in Bone Morphogenetic Proteins.通过骨形态发生蛋白的顺式调控变化演化出新的骨骼特征
Cell. 2016 Jan 14;164(1-2):45-56. doi: 10.1016/j.cell.2015.12.007. Epub 2016 Jan 7.
2
Signaling networks organizing regenerative growth of the zebrafish fin.组织斑马鱼鳍再生生长的信号网络。
Trends Genet. 2015 Jun;31(6):336-43. doi: 10.1016/j.tig.2015.03.012. Epub 2015 Apr 27.
3
A distinct regulatory region of the Bmp5 locus activates gene expression following adult bone fracture or soft tissue injury.
将转基因表达靶向损伤小鼠心肌的增强子-腺相关病毒载体的空间和纵向追踪
bioRxiv. 2025 Jul 9:2025.04.28.651096. doi: 10.1101/2025.04.28.651096.
4
Aiming for spatial and temporal control of gene expression.旨在实现基因表达的时空控制。
Elife. 2025 Jul 10;14:e107945. doi: 10.7554/eLife.107945.
5
Cardiac Regeneration and Repair in Zebrafish and Mammalian Models.斑马鱼和哺乳动物模型中的心脏再生与修复
Curr Cardiol Rep. 2025 Jun 17;27(1):95. doi: 10.1007/s11886-025-02235-6.
6
Sequential activation of transcription factors promotes liver regeneration through specific and developmental enhancers.转录因子的顺序激活通过特定的发育增强子促进肝脏再生。
Cell Genom. 2025 Jul 9;5(7):100887. doi: 10.1016/j.xgen.2025.100887. Epub 2025 May 22.
7
Targeting the Hippo Pathway for Cardiac Regeneration.靶向河马通路促进心脏再生
Physiology (Bethesda). 2025 Nov 1;40(6):0. doi: 10.1152/physiol.00003.2025. Epub 2025 May 13.
8
Blueprints for healing: central nervous system regeneration in zebrafish and neonatal mice.愈合蓝图：斑马鱼和新生小鼠的中枢神经系统再生
BMC Biol. 2025 Apr 30;23(1):115. doi: 10.1186/s12915-025-02203-0.
9
Cardiac enhancers: Gateway to the regulatory mechanisms of heart regeneration.心脏增强子：通向心脏再生调控机制的大门。
Semin Cell Dev Biol. 2025 Jun;170:103610. doi: 10.1016/j.semcdb.2025.103610. Epub 2025 Apr 10.
10
Mild cryoinjury in zebrafish fin induces regenerative response without blastema formation.斑马鱼鳍的轻度冷冻损伤可诱导再生反应，但不会形成芽基。
Dev Growth Differ. 2025 Apr;67(3):174-181. doi: 10.1111/dgd.12962. Epub 2025 Feb 1.
Bmp5基因座的一个独特调控区域在成年骨折或软组织损伤后激活基因表达。
Bone. 2015 Aug;77:31-41. doi: 10.1016/j.bone.2015.04.010. Epub 2015 Apr 14.
4
Neuregulin stimulation of cardiomyocyte regeneration in mice and human myocardium reveals a therapeutic window.神经调节蛋白对小鼠和人类心肌中心肌细胞再生的刺激揭示了一个治疗窗口期。
Sci Transl Med. 2015 Apr 1;7(281):281ra45. doi: 10.1126/scitranslmed.aaa5171.
5
Nrg1 is an injury-induced cardiomyocyte mitogen for the endogenous heart regeneration program in zebrafish.神经调节蛋白1（Nrg1）是一种损伤诱导的心肌细胞有丝分裂原，用于斑马鱼体内的心脏再生程序。
Elife. 2015 Apr 1;4:e05871. doi: 10.7554/eLife.05871.
6
A large genomic deletion leads to enhancer adoption by the lamin B1 gene: a second path to autosomal dominant adult-onset demyelinating leukodystrophy (ADLD).一个大的基因组缺失导致层粘连蛋白B1基因采用增强子：常染色体显性成人起病型脱髓鞘性脑白质营养不良（ADLD）的第二条途径。
Hum Mol Genet. 2015 Jun 1;24(11):3143-54. doi: 10.1093/hmg/ddv065. Epub 2015 Feb 20.
7
Integrative analysis of 111 reference human epigenomes.111 个人类参考基因组的综合分析。
Nature. 2015 Feb 19;518(7539):317-30. doi: 10.1038/nature14248.
8
Enhancer evolution across 20 mammalian species.20种哺乳动物物种的增强子进化
Cell. 2015 Jan 29;160(3):554-66. doi: 10.1016/j.cell.2015.01.006.
9
Long-range gene regulation and novel therapeutic applications.长程基因调控和新的治疗应用。
Blood. 2015 Mar 5;125(10):1521-5. doi: 10.1182/blood-2014-11-567925. Epub 2015 Jan 23.
10
Convergent evolution of complex regulatory landscapes and pleiotropy at Hox loci.Hox 基因座复杂调控景观和多效性的趋同进化。
Science. 2014 Nov 21;346(6212):1004-6. doi: 10.1126/science.1257493.