MiR‐133 promotes cardiac reprogramming by directly repressing Snai1 and silencing fibroblast signatures

Muraoka, Naoto; Yamakawa, Hiroyuki; Miyamoto, Kazuaki; Sadahiro, Taketaro; Umei, Tomohiko; Isomi, Mari; Nakashima, Hanae; Akiyama, Mizuha; Wada, Rie; Inagawa, Kohei; Nishiyama, Takahiko; Kaneda, Ruri; Fukuda, Tsuyoshi; Takeda, Satoshi; Tohyama, Shugo; Hashimoto, Hisayuki; Kawamura, Yoshifumi; Goshima, Naoki; Aeba, Ryo; Yamagishi, Hiroyuki; Fukuda, Keiichi; Ieda, Masaki

doi:10.15252/embj.201387605

Cited by 283 publications

(285 citation statements)

References 29 publications

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“…These stimulated cells expressed cardiac specific proteins and showed spontaneous contractility, emphasizing the role of these miRs in the control of specific cell development programs via the modulation of specific factor targets. Further, both human and mouse fibroblasts can be reprogrammed to form cardiomyocyte-like cells by overexpression of cardiac transcription factors (Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Mesp1 and Myocd) along with miR 133a, which directly represses Snai1 which normally regulates EMT processes [16] . Interestingly, exogenous miR133b can also downregulate Snai1 expression, suppressing fibroblast genes and upregulate the expression of a number of characteristic cardiac cell genes in vitro, yet it cannot replace miR133a during normal heart development in vivo.…”

Section: Cardiac Myogenesismentioning

confidence: 99%

Roles of the canonical myomiRs miR-1, -133 and -206 in cell development and disease

Mitchelson¹

2015

WJBC

139

132

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MicroRNAs are small non-coding RNAs that participate in different biological processes, providing subtle combinational regulation of cellular pathways, often by regulating components of signalling pathways. Aberrant expression of miRNAs is an important factor in the development and progression of disease. The canonical myomiRs (miR-1, -133 and -206) are central to the development and health of mammalian skeletal and cardiac muscles, but new findings show they have regulatory roles in the development of other mammalian non-muscle tissues, including nerve, brain structures, adipose and some specialised immunological cells. Moreover, the deregulation of myomiR expression is associated with a variety of different cancers, where typically they have tumor suppressor functions, although examples of an oncogenic role illustrate their diverse function in different cell environments. This review examines the involvement of the related myomiRs at the crossroads between cell development/ tissue regeneration/tissue inflammation responses, and cancer development. Core tip: The roles of the canonical muscle-associated microRNAs are reviewed, including microRNA families miR-1 and miR-133, and single miR-206, which are collectively known as the "myomiRs". The myomiRs act at the crossroads of the molecular regulation of muscle cells, linking between pathways for cell differentiation, development and maintenance, but also potentiate aberrant cell growth in numerous non-muscle cancers. Typically myomiRs are downregulated in cancers, but some myomiRs are upregulated in a few cancers, yet each dysregulation event advances tumor progression. The review examines normal and disease-linked molecular changes associated with the myomiRs, and collates the extensive literature into accessible tables. REVIEW

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Section: Cardiac Myogenesismentioning

confidence: 99%

Roles of the canonical myomiRs miR-1, -133 and -206 in cell development and disease

Mitchelson¹

2015

WJBC

139

132

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“…1 Subsequently, multiple groups have achieved and improved direct cardiac reprogramming from mouse and human fibroblasts by overexpressing other combinations of cardiac transcription factors and cardiac-enriched miRNAs. [2][3][4][5][6][7][8][9] Intriguingly, it was reported that gene delivery of reprogramming factors into mouse infarcted hearts converted endogenous CFs into functional iCMs, reduced scar size, and improved cardiac function after myocardial infarction. 4,10,11 Although these recent achievements are promising, the low reprogramming efficiency of fully reprogrammed functional iCMs and the reproducibility of cardiac reprogramming continue to be controversial aspects of this technology.…”

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confidence: 99%

Stoichiometry of Transcription Factors Is Critical for Cardiac Reprogramming

Muraoka

Ieda

2015

Circulation Research

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“…Furthermore, we found that miR-133-mediated Snai1 repression was critical for cardiac reprogramming in adult mouse (and human cardiac) fibroblasts, and that silencing fibroblast signatures via miR-133/Snai1 was a key molecular roadblock during cardiac reprogramming. 18) Importantly, this is a first study demonstrating a molecular mechanism underlying cardiac reprogramming by defined factors. Generation of human iCMs: In 2013, three studies including ours applied the concept of direct reprogramming to neonatal and adult human fibroblasts.…”

Section: Direct Cardiac Reprogramming In Vitromentioning

confidence: 85%

Strategies for Heart Regeneration

Yamakawa¹,

Ieda

2015

Int. Heart J.

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SummaryCardiovascular disease remains a leading cause of death for which current therapeutic regimens are limited. Following myocardial injury, endogenous cardiac fibroblasts, which account for more than half of the cells in the heart, proliferate and synthesize extracellular matrix, leading to fibrosis and heart failure. As terminally differentiated cardiomyocytes have little regenerative capacity following injury, development of cardiac regenerative therapy is highly desired. Embryonic stem (ES) and induced pluripotent stem (iPS) cells are promising tools for regenerative medicine; however, these stem cells demonstrate variable cardiac differentiation efficiency and tumorigenicity, which should be solved for clinical applications. Up until the last decade, it was an established theory that cardiomyocytes could only be produced from fibroblasts mediating through stem cells. However, in 2010, we reported for the first time a novel method of the direct reprogramming of fibroblasts into cardiomyocytes, demonstrating various reprogramming pathways exist. This review summarizes the latest trends in stem cell and regenerative research, touching upon iPS cells, partial reprogramming strategy, and direct cardiac reprogramming. Specifically, we examine the many recent advances in both in vitro and in vivo direct cardiac reprogramming, and explore the application of these methods to cardiovascular regenerative medicine. (Int Heart J 2015; 56: 1-5)

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MiR‐133 promotes cardiac reprogramming by directly repressing Snai1 and silencing fibroblast signatures

Cited by 283 publications

References 29 publications

Roles of the canonical myomiRs miR-1, -133 and -206 in cell development and disease

Roles of the canonical myomiRs miR-1, -133 and -206 in cell development and disease

Stoichiometry of Transcription Factors Is Critical for Cardiac Reprogramming

Strategies for Heart Regeneration

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