• 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

Lin28-TNFR2 信号在心脏干细胞激活和分化中的关键作用。

Critical role of Lin28-TNFR2 signalling in cardiac stem cell activation and differentiation.

机构信息

Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.

Translational Medicine Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.

出版信息

J Cell Mol Med. 2019 Apr;23(4):0. doi: 10.1111/jcmm.14202. Epub 2019 Feb 7.

DOI:10.1111/jcmm.14202
PMID:30734494
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6433861/
Abstract

Tumour necrotic factor receptor-2 (TNFR2) has been to be cardiac-protective and is expressed in cardiac progenitor cells. Our goal is to define the mechanism for TNFR2-mediated cardiac stem cell activation and differentiation. By employing a protocol of in vitro cardiac stem cell (CSC) differentiation from human inducible pluripotent stem cell (hiPSC), we show that expression of TNFR2 precedes expression of CSC markers followed by expression of mature cardiomyocyte proteins. Activation of TNFR2 by a specific agonist promotes whereas inhibition of TNFR2 by neutralizing antibody diminishes hiPSC-based CSC differentiation. Interestingly, pluripotent cell factor RNA-binding protein Lin28 enhances TNFR2 protein expression in early CSC activation by directly binding to a conserved Lin28-motif within the 3'UTR of Tnfr2 mRNA. Furthermore, inhibition of Lin28 blunts TNFR2 expression and TNFR2-dependent CSC activation and differentiation. Our study demonstrates a critical role of Lin28-TNFR2 axis in CSC activation and survival, providing a novel strategy to enhance stem cell-based therapy for the ischaemic heart diseases.

摘要

肿瘤坏死因子受体-2（TNFR2）具有心脏保护作用，并在心脏祖细胞中表达。我们的目标是确定 TNFR2 介导的心脏干细胞激活和分化的机制。通过采用体外心脏干细胞（CSC）从人诱导多能干细胞（hiPSC）分化的方案，我们表明 TNFR2 的表达先于 CSC 标志物的表达，然后是成熟心肌蛋白的表达。TNFR2 的特异性激动剂激活促进，而中和抗体抑制 TNFR2 则减少基于 hiPSC 的 CSC 分化。有趣的是，多能细胞因子 RNA 结合蛋白 Lin28 通过直接结合 Tnfr2 mRNA 3'UTR 中的保守 Lin28 基序增强早期 CSC 激活中的 TNFR2 蛋白表达。此外，抑制 Lin28 会使 TNFR2 表达和 TNFR2 依赖性 CSC 激活和分化减弱。我们的研究表明 Lin28-TNFR2 轴在 CSC 激活和存活中起关键作用，为缺血性心脏病的基于干细胞的治疗提供了一种新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5593/6433861/b8ef27042dfd/JCMM-23-2943-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5593/6433861/dfe815468423/JCMM-23-2943-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5593/6433861/00ce9f8f44d4/JCMM-23-2943-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5593/6433861/08566344ecf9/JCMM-23-2943-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5593/6433861/0c6e88c4330d/JCMM-23-2943-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5593/6433861/b929d7d3e098/JCMM-23-2943-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5593/6433861/e61aaab94df4/JCMM-23-2943-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5593/6433861/b8ef27042dfd/JCMM-23-2943-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5593/6433861/dfe815468423/JCMM-23-2943-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5593/6433861/00ce9f8f44d4/JCMM-23-2943-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5593/6433861/08566344ecf9/JCMM-23-2943-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5593/6433861/0c6e88c4330d/JCMM-23-2943-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5593/6433861/b929d7d3e098/JCMM-23-2943-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5593/6433861/e61aaab94df4/JCMM-23-2943-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5593/6433861/b8ef27042dfd/JCMM-23-2943-g007.jpg

相似文献

1
Critical role of Lin28-TNFR2 signalling in cardiac stem cell activation and differentiation.Lin28-TNFR2 信号在心脏干细胞激活和分化中的关键作用。
J Cell Mol Med. 2019 Apr;23(4):0. doi: 10.1111/jcmm.14202. Epub 2019 Feb 7.
2
TNF receptor signaling inhibits cardiomyogenic differentiation of cardiac stem cells and promotes a neuroadrenergic-like fate.肿瘤坏死因子受体信号传导抑制心脏干细胞的心肌分化，并促进类似神经肾上腺素能的命运。
Am J Physiol Heart Circ Physiol. 2016 Nov 1;311(5):H1189-H1201. doi: 10.1152/ajpheart.00904.2015. Epub 2016 Sep 2.
3
TNF, acting through inducibly expressed TNFR2, drives activation and cell cycle entry of c-Kit+ cardiac stem cells in ischemic heart disease.TNF 通过诱导表达的 TNFR2 驱动缺血性心脏病中 c-Kit+ 心脏干细胞的激活和细胞周期进入。
Stem Cells. 2013 Sep;31(9):1881-92. doi: 10.1002/stem.1433.
4
A Comparative Assessment of Marker Expression Between Cardiomyocyte Differentiation of Human Induced Pluripotent Stem Cells and the Developing Pig Heart.人诱导多能干细胞心肌细胞分化与猪心脏发育过程中标志物表达的比较评估
Stem Cells Dev. 2021 Apr 1;30(7):374-385. doi: 10.1089/scd.2020.0184.
5
Both internalization and AIP1 association are required for tumor necrosis factor receptor 2-mediated JNK signaling.肿瘤坏死因子受体 2 介导的 JNK 信号通路需要内化和 AIP1 相关联。
Arterioscler Thromb Vasc Biol. 2012 Sep;32(9):2271-9. doi: 10.1161/ATVBAHA.112.253666. Epub 2012 Jun 28.
6
Role of alpha- and beta-adrenergic receptors in cardiomyocyte differentiation from murine-induced pluripotent stem cells.α-和β-肾上腺素能受体在小鼠诱导多能干细胞向心肌细胞分化中的作用。
Cell Prolif. 2017 Feb;50(1). doi: 10.1111/cpr.12310. Epub 2016 Oct 27.
7
Tumorigenicity assay essential for facilitating safety studies of hiPSC-derived cardiomyocytes for clinical application.肿瘤形成能力分析对于促进用于临床应用的 hiPSC 衍生心肌细胞的安全性研究至关重要。
Sci Rep. 2019 Feb 13;9(1):1881. doi: 10.1038/s41598-018-38325-5.
8
TNFR1 and TNFR2 signaling interplay in cardiac myocytes.心肌细胞中肿瘤坏死因子受体1（TNFR1）与肿瘤坏死因子受体2（TNFR2）信号转导的相互作用
J Biol Chem. 2007 Dec 7;282(49):35564-73. doi: 10.1074/jbc.M704003200. Epub 2007 Oct 2.
9
Construction of a vascularized hydrogel for cardiac tissue formation in a porcine model.构建用于在猪模型中形成心脏组织的血管化水凝胶。
J Tissue Eng Regen Med. 2018 Apr;12(4):e2029-e2038. doi: 10.1002/term.2634. Epub 2018 Jan 10.
10
Epigenetic Priming of Human Pluripotent Stem Cell-Derived Cardiac Progenitor Cells Accelerates Cardiomyocyte Maturation.人类多能干细胞衍生的心脏祖细胞的表观遗传启动加速心肌细胞成熟。
Stem Cells. 2019 Jul;37(7):910-923. doi: 10.1002/stem.3021. Epub 2019 May 14.

引用本文的文献

1
Understanding the role of TNFR2 signaling in the tumor microenvironment of breast cancer.了解 TNFR2 信号在乳腺癌肿瘤微环境中的作用。
J Exp Clin Cancer Res. 2024 Nov 28;43(1):312. doi: 10.1186/s13046-024-03218-1.
2
Influence of acidic metabolic environment on differentiation of stem cell-derived cardiomyocytes.酸性代谢环境对干细胞源性心肌细胞分化的影响。
Front Cardiovasc Med. 2024 Mar 20;11:1288710. doi: 10.3389/fcvm.2024.1288710. eCollection 2024.
3
The generation of a lactate-rich environment stimulates cell cycle progression and modulates gene expression on neonatal and hiPSC-derived cardiomyocytes.

本文引用的文献

1
STAT3-Inducible Mouse ESCs: A Model to Study the Role of STAT3 in ESC Maintenance and Lineage Differentiation.STAT3诱导的小鼠胚胎干细胞：一种研究STAT3在胚胎干细胞维持和谱系分化中作用的模型。
Stem Cells Int. 2018 Sep 4;2018:8632950. doi: 10.1155/2018/8632950. eCollection 2018.
2
Lin28 is induced in primed embryonic stem cells and regulates let-7-independent events.Lin28在启动态胚胎干细胞中被诱导表达，并调控不依赖于let-7的事件。
FASEB J. 2017 Mar;31(3):1046-1058. doi: 10.1096/fj.201600848R. Epub 2016 Dec 5.
3
TNF receptor signaling inhibits cardiomyogenic differentiation of cardiac stem cells and promotes a neuroadrenergic-like fate.
产生富含乳酸的环境会刺激细胞周期进程，并调节新生儿和 hiPSC 衍生的心肌细胞的基因表达。
Biomater Adv. 2022 Aug;139:213035. doi: 10.1016/j.bioadv.2022.213035. Epub 2022 Jul 20.
4
The Roles of TNFR2 Signaling in Cancer Cells and the Tumor Microenvironment and the Potency of TNFR2 Targeted Therapy.TNFR2 信号在癌细胞和肿瘤微环境中的作用及 TNFR2 靶向治疗的效力。
Cells. 2022 Jun 17;11(12):1952. doi: 10.3390/cells11121952.
5
Exogenous LIN28 Is Required for the Maintenance of Self-Renewal and Pluripotency in Presumptive Porcine-Induced Pluripotent Stem Cells.外源性LIN28是维持猪诱导多能干细胞自我更新和多能性所必需的。
Front Cell Dev Biol. 2021 Jul 20;9:709286. doi: 10.3389/fcell.2021.709286. eCollection 2021.
肿瘤坏死因子受体信号传导抑制心脏干细胞的心肌分化，并促进类似神经肾上腺素能的命运。
Am J Physiol Heart Circ Physiol. 2016 Nov 1;311(5):H1189-H1201. doi: 10.1152/ajpheart.00904.2015. Epub 2016 Sep 2.
4
LIN28: roles and regulation in development and beyond.LIN28：在发育及其他方面的作用与调控
Development. 2015 Jul 15;142(14):2397-404. doi: 10.1242/dev.117580.
5
The Association Between p38 MAPK-Mediated TNF-α/TNFR2 up-Regulation and 2-(4-Aminophenyl)-7-Methoxybenzothiazole-Induced Apoptosis in Human Leukemia U937 Cells.p38MAPK 介导的 TNF-α/TNFR2 上调与 2-(4-氨基苯基)-7-甲氧基苯并噻唑诱导的人白血病 U937 细胞凋亡之间的关系。
J Cell Physiol. 2016 Jan;231(1):130-41. doi: 10.1002/jcp.25064.
6
A novel mechanism of LIN-28 regulation of let-7 microRNA expression revealed by in vivo HITS-CLIP in C. elegans.秀丽隐杆线虫体内HITS-CLIP技术揭示LIN-28调控let-7微小RNA表达的新机制。
RNA. 2015 May;21(5):985-96. doi: 10.1261/rna.045542.114. Epub 2015 Mar 24.
7
AIP1-mediated stress signaling in atherosclerosis and arteriosclerosis.AIP1介导的动脉粥样硬化和动脉硬化中的应激信号传导。
Curr Atheroscler Rep. 2015 May;17(5):503. doi: 10.1007/s11883-015-0503-z.
8
Akt1 signaling coordinates BMP signaling and β-catenin activity to regulate second heart field progenitor development.Akt1信号传导协调骨形态发生蛋白（BMP）信号传导和β-连环蛋白活性，以调节第二心脏场祖细胞的发育。
Development. 2015 Feb 15;142(4):732-42. doi: 10.1242/dev.119016.
9
Cell therapy for heart failure: a comprehensive overview of experimental and clinical studies, current challenges, and future directions.细胞疗法治疗心力衰竭：实验和临床研究的全面综述、当前挑战和未来方向。
Circ Res. 2013 Aug 30;113(6):810-34. doi: 10.1161/CIRCRESAHA.113.300219.
10
A HCN4+ cardiomyogenic progenitor derived from the first heart field and human pluripotent stem cells.来源于头褶心区的 HCN4+ 心肌祖细胞和人类多能干细胞。
Nat Cell Biol. 2013 Sep;15(9):1098-106. doi: 10.1038/ncb2824. Epub 2013 Aug 25.