Suppr超能文献

Chibby是Wnt/β-连环蛋白信号通路的拮抗剂,可促进小鼠胚胎干细胞向心肌细胞分化。

Chibby, an antagonist of the Wnt/beta-catenin pathway, facilitates cardiomyocyte differentiation of murine embryonic stem cells.

作者信息

Singh Amar M, Li Feng-Qian, Hamazaki Takashi, Kasahara Hideko, Takemaru Ken-ichi, Terada Naohiro

机构信息

Department of Pathology, University of Florida College of Medicine, Box 100275, Gainesville, FL 32610, USA.

出版信息

Circulation. 2007 Feb 6;115(5):617-26. doi: 10.1161/CIRCULATIONAHA.106.642298. Epub 2007 Jan 29.

Abstract

BACKGROUND

Embryonic stem cell (ESC)-derived cardiomyocytes are anticipated to serve as a useful source for future cell-based cardiovascular disease therapies. Research emphasis is currently focused on determining methods to direct the differentiation of ESCs to a large population of cardiomyocytes with high purity. To this aim, understanding the molecular mechanisms that control ESC-to-cardiomyocyte differentiation should play a critical role in the development of this methodology. The Wnt/beta-catenin signaling pathway has been implicated in both embryonic cardiac development and in vitro ESC differentiation into cardiomyocytes. Chibby is a recently identified nuclear protein that directly binds to beta-catenin and antagonizes its transcriptional activity.

METHODS AND RESULTS

Chibby was ubiquitously expressed in early stages of ESC differentiation but upregulated during cardiomyocyte specification. Of interest, the Chibby gene promoter has multiple binding sites for the cardiac-specific homeodomain protein Nkx2.5, and its promoter activity was indeed positively regulated by Nkx2.5. Furthermore, overexpression of Chibby increased cardiac differentiation of ESCs, whereas loss of Chibby by RNAi impaired cardiomyocyte differentiation.

CONCLUSIONS

These data illustrate the regulation and function of Chibby in facilitating cardiomyocyte differentiation from ESCs. By revealing molecular mechanisms that control ESC-to-cardiomyocyte differentiation, this study will allow for the future development of technologies to improve cardiomyocyte differentiation from ESCs.

摘要

背景

胚胎干细胞(ESC)来源的心肌细胞有望成为未来基于细胞的心血管疾病治疗的有用来源。目前研究重点集中在确定将胚胎干细胞定向分化为大量高纯度心肌细胞的方法。为实现这一目标,了解控制胚胎干细胞向心肌细胞分化的分子机制对于该方法的开发应起到关键作用。Wnt/β-连环蛋白信号通路已被证明与胚胎心脏发育以及体外胚胎干细胞分化为心肌细胞有关。Chibby是最近发现的一种核蛋白,它直接与β-连环蛋白结合并拮抗其转录活性。

方法与结果

Chibby在胚胎干细胞分化的早期阶段广泛表达,但在心肌细胞特化过程中上调。有趣的是,Chibby基因启动子有多个心脏特异性同源结构域蛋白Nkx2.5的结合位点,其启动子活性确实受到Nkx2.5的正向调控。此外,Chibby的过表达增加了胚胎干细胞的心脏分化,而通过RNA干扰使Chibby缺失则损害了心肌细胞的分化。

结论

这些数据阐明了Chibby在促进胚胎干细胞向心肌细胞分化中的调控作用和功能。通过揭示控制胚胎干细胞向心肌细胞分化的分子机制,本研究将为未来改进胚胎干细胞向心肌细胞分化的技术发展提供可能。

相似文献

1
Chibby, an antagonist of the Wnt/beta-catenin pathway, facilitates cardiomyocyte differentiation of murine embryonic stem cells.
Circulation. 2007 Feb 6;115(5):617-26. doi: 10.1161/CIRCULATIONAHA.106.642298. Epub 2007 Jan 29.
2
Temporal modulation of β-catenin signaling by multicellular aggregation kinetics impacts embryonic stem cell cardiomyogenesis.
Stem Cells Dev. 2013 Oct 1;22(19):2665-77. doi: 10.1089/scd.2013.0007. Epub 2013 Jun 14.
4
Chibby promotes adipocyte differentiation through inhibition of beta-catenin signaling.
Mol Cell Biol. 2007 Jun;27(12):4347-54. doi: 10.1128/MCB.01640-06. Epub 2007 Apr 2.
7
Reduced expression of beta-catenin inhibitor Chibby in colon carcinoma cell lines.
World J Gastroenterol. 2006 Mar 14;12(10):1529-35. doi: 10.3748/wjg.v12.i10.1529.
10
Transmembrane protein 88: a Wnt regulatory protein that specifies cardiomyocyte development.
Development. 2013 Sep;140(18):3799-808. doi: 10.1242/dev.094789. Epub 2013 Aug 7.

引用本文的文献

1
A genome-wide CRISPR screen identifies BRD4 as a regulator of cardiomyocyte differentiation.
Nat Cardiovasc Res. 2024 Mar;3(3):317-331. doi: 10.1038/s44161-024-00431-1. Epub 2024 Feb 23.
4
5
Anti-oncogenic activity of Chibby in the development of human nasopharyngeal carcinoma.
Oncol Lett. 2018 Apr;15(4):5849-5858. doi: 10.3892/ol.2018.8009. Epub 2018 Feb 9.
7
Distinctive Roles of Canonical and Noncanonical Wnt Signaling in Human Embryonic Cardiomyocyte Development.
Stem Cell Reports. 2016 Oct 11;7(4):764-776. doi: 10.1016/j.stemcr.2016.08.008. Epub 2016 Sep 15.
8
Pluripotent Stem Cells and DNA Damage Response to Ionizing Radiations.
Radiat Res. 2016 Jul;186(1):17-26. doi: 10.1667/RR14417.1. Epub 2016 Jun 22.
9
HoxBlinc RNA Recruits Set1/MLL Complexes to Activate Hox Gene Expression Patterns and Mesoderm Lineage Development.
Cell Rep. 2016 Jan 5;14(1):103-114. doi: 10.1016/j.celrep.2015.12.007. Epub 2015 Dec 24.
10
Chibby functions in Xenopus ciliary assembly, embryonic development, and the regulation of gene expression.
Dev Biol. 2014 Nov 15;395(2):287-98. doi: 10.1016/j.ydbio.2014.09.008. Epub 2014 Sep 16.

本文引用的文献

1
Canonical Wnt signaling is required for development of embryonic stem cell-derived mesoderm.
Development. 2006 Oct;133(19):3787-96. doi: 10.1242/dev.02551. Epub 2006 Aug 30.
2
Sequential development of hematopoietic and cardiac mesoderm during embryonic stem cell differentiation.
Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13170-5. doi: 10.1073/pnas.0501672102. Epub 2005 Sep 2.
3
Prospective identification of cardiac progenitors by a novel single cell-based cardiomyocyte induction.
FASEB J. 2005 Sep;19(11):1534-6. doi: 10.1096/fj.04-3540fje. Epub 2005 Jul 20.
4
Embryonic stem cell differentiation: emergence of a new era in biology and medicine.
Genes Dev. 2005 May 15;19(10):1129-55. doi: 10.1101/gad.1303605.
5
6
Non-canonical Wnt signaling enhances differentiation of human circulating progenitor cells to cardiomyogenic cells.
J Biol Chem. 2005 Apr 29;280(17):16838-42. doi: 10.1074/jbc.M500323200. Epub 2005 Feb 8.
7
Heart induction by Wnt antagonists depends on the homeodomain transcription factor Hex.
Genes Dev. 2005 Feb 1;19(3):387-96. doi: 10.1101/gad.1279405.
8
Quercetin, a potent inhibitor against beta-catenin/Tcf signaling in SW480 colon cancer cells.
Biochem Biophys Res Commun. 2005 Mar 4;328(1):227-34. doi: 10.1016/j.bbrc.2004.12.151.
9
Wnt11 facilitates embryonic stem cell differentiation to Nkx2.5-positive cardiomyocytes.
Biochem Biophys Res Commun. 2004 Dec 17;325(3):968-75. doi: 10.1016/j.bbrc.2004.10.103.
10
Aggregation of embryonic stem cells induces Nanog repression and primitive endoderm differentiation.
J Cell Sci. 2004 Nov 1;117(Pt 23):5681-6. doi: 10.1242/jcs.01489. Epub 2004 Oct 19.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验