<i>Tbx20</i>
            Is Required in Mid-Gestation Cardiomyocytes and Plays a Central Role in Atrial Development

Boogerd, Cornelis J.; Zhu, Xiaoming; Aneas, Ivy; Sakabe, Noboru Jo; Zhang, Lunfeng; Sobreira, Débora R.; Montefiori, Lindsey E.; Bogomolovas, Julius; Joslin, Amelia C; Zhou, Bin; Chen, Ju; Nóbrega, Marcelo A.; Evans, Sylvia M.

doi:10.1161/circresaha.118.311339

Cited by 45 publications

(40 citation statements)

References 67 publications

(96 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This provides an excellent in vitro model for studying various molecular mechanisms of heart. Cardiomyocyte culture has become a basic method for investigating cardiac physiology and pathology, and it provides an ideal model for the study of heart development, differentiation, and metabolism (Boogerd et al 2018 ). Therefore, the cultivation of cardiomyocytes has gradually become a useful model for studying myocardial injury (Liu et al 2018 ).…”

Section: Discussionmentioning

confidence: 99%

COX6B1 relieves hypoxia/reoxygenation injury of neonatal rat cardiomyocytes by regulating mitochondrial function

et al. 2018

View full text Add to dashboard Cite

ObjectiveMitochondrial dysfunction plays a pivotal role in various pathophysiological processes of heart. Cytochrome oxidase subunit 6B1 (COX6B1) is a subunit of cytochrome oxidase.MethodsCardiomyocytes were isolated from neonatal SD rats (within 24 h of birth) by repeating digestion of collagenase and trypsin. COX6B1 over-expression and hypoxia/reoxygenation was conducted on neonatal rat cardiomyocytes. Cell viability, apoptosis rates, mitochondria membrane potential and mitochondrial permeabilization transition pores (mPTPs) were then determined respectively by Cell performing Counting Kit-8 (CCK-8), Annexin-V/PI assay, JC-1 assay, mPTP assay. The expression of cyto C and apoptosis-related factors were detected by RT-Qpcr and Western blot.ResultsHypoxia/reoxygenation increased apoptosis and mPTP levels, and decreased mitochondria membrane potential in I/R and I/R + EV groups. COX6B1 over-expression increased mitochondria cyto C, pro-caspase-3, pro-caspase-9 and bcl-2, while it decreased cytosol cyto C, cleaved-caspase-3, cleaved-caspase-9 and bax compared to I/R + EV group.ConclusionCOX6B1 protected cardiomyocytes from hypoxia/reoxygenation injury by reducing ROS production and cell apoptosis, during which reduction of the release of cytochrome C from mitochondria to cytosol was involved. Our study demonstrated that COX6B1 may be an candidate target gene in preventing hypoxia/reoxygenation injury of cardiomyocytes.

show abstract

Section: Discussionmentioning

confidence: 99%

COX6B1 relieves hypoxia/reoxygenation injury of neonatal rat cardiomyocytes by regulating mitochondrial function

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Interestingly, we find that tbx20 induction is not only localized to the injured myocardium, but also detectable in the atrial epicardium following ventricle injury. During development, tbx20 is expressed in epicardial cells surrounding the atrioventricular canal groove (Yamagishi et al, 2004;Boogerd et al, 2018), but the function of epicardial tbx20 is still unclear. Previous studies indicate that epicardium is required for heart regeneration in zebrafish (Kikuchi et al, 2011a;Wang et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Tbx20 Induction Promotes Zebrafish Heart Regeneration by Inducing Cardiomyocyte Dedifferentiation and Endocardial Expansion

Fang

Lai

She

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Heart regeneration requires replenishment of lost cardiomyocytes (CMs) and cells of the endocardial lining. However, the signaling regulation and transcriptional control of myocardial dedifferentiation and endocardial activation are incompletely understood during cardiac regeneration. Here, we report that T-Box Transcription Factor 20 (Tbx20) is induced rapidly in the myocardial wound edge in response to various sources of cardiac damages in zebrafish. Inducing Tbx20 specifically in the adult myocardium promotes injury-induced CM proliferation through CM dedifferentiation, leading to loss of CM cellular contacts and re-expression of cardiac embryonic or fetal gene programs. Unexpectedly, we identify that myocardial Tbx20 induction activates the endocardium at the injury site with enhanced endocardial cell extension and proliferation, where it induces the endocardial Bone morphogenetic protein 6 (Bmp6) signaling. Pharmacologically inactivating endocardial Bmp6 signaling reduces expression of its targets, Id1 and Id2b, attenuating the increased endocardial regeneration in tbx20overexpressing hearts. Altogether, our study demonstrates that Tbx20 induction promotes adult heart regeneration by inducing cardiomyocyte dedifferentiation as well as non-cell-autonomously enhancing endocardial cell regeneration.

show abstract

“…Recent research has shown that TBX20, a member of the Tbox transcription factor family plays also a key role in atrial development [50]. Tbx20 function in ventricular cardiac myocytes has been investigated earlier.…”

Section: Transcription Factors Involved In Atrial Development and Dismentioning

confidence: 99%

“…While overexpression of Tbx20 in adult cardiac myocytes induced proliferation and improved cardiac function after myocardial infarction [52]. Besides the directly activating function of myocyte proliferation genes, Boogerd et al showed that Tbx20 directly represses a cardiac progenitor gene program in cardiac myocytes and activates atrial and ventricular specific genes for the establishment or maintenance of atrial and ventricular identity [50]. Interestingly, at E10.5 and E11.5, atria from Tbx20 cKO mice showed reduced levels of COUP-TFII.…”

Section: Transcription Factors Involved In Atrial Development and Dismentioning

confidence: 99%

“…Interestingly, at E10.5 and E11.5, atria from Tbx20 cKO mice showed reduced levels of COUP-TFII. Moreover, Boogerd et al could show that Tbx20 binds an enhancer upstream of COUP-TFII, which regulates its expression in atrial cardiac myocytes while Tbx20 might establish ventricular identity by direct regulation of Hey2 and Irx4 in developing ventricular cardiac myocytes [50].…”

Section: Transcription Factors Involved In Atrial Development and Dismentioning

confidence: 99%

See 1 more Smart Citation

Four Dimensions of the Cardiac Myocyte Epigenome: from Fetal to Adult Heart

Rommel

Hein

2020

Curr Cardiol Rep

View full text Add to dashboard Cite

Purpose of Review Development, physiological growth and the response of the heart to injury are accompanied by changes of the transcriptome and epigenome of cardiac myocytes. Recently, cell sorting and next generation sequencing techniques have been applied to determine cardiac myocyte-specific transcriptional and epigenetic mechanisms. This review provides a comprehensive overview of studies analysing the transcriptome and epigenome of cardiac myocytes in mouse and human hearts during development, physiological growth and disease. Recent Findings Adult cardiac myocytes express > 12,600 genes, and their expression levels correlate positively with active histone marks and inversely with gene body DNA methylation. DNA methylation accompanied the perinatal switch in sarcomere or metabolic isoform gene expression in cardiac myocytes, but remained rather stable in heart disease. DNA methylation and histone marks identified > 100,000 cis-regulatory regions in the cardiac myocyte epigenome with a dynamic spectrum of transcription factor binding sites. The ETS-related transcription factor ETV1 was identified as an atrial-specific element involved in the pathogenesis of atrial fibrillation. Summary Thus, dynamic development of the atrial vs. ventricular cardiac myocyte epigenome provides a basis to identify location and time-dependent mechanisms of epigenetic control to shape pathological gene expression during heart disease. Identifying the four dimensions of the cardiac myocyte epigenome, atrial vs. ventricular location, time during development and growth, and disease-specific signals, may ultimately lead to new treatment strategies for heart disease.

show abstract

Tbx20 Is Required in Mid-Gestation Cardiomyocytes and Plays a Central Role in Atrial Development

Abstract: Supplemental Digital Content is available in the text.

Cited by 45 publications

References 67 publications

COX6B1 relieves hypoxia/reoxygenation injury of neonatal rat cardiomyocytes by regulating mitochondrial function

COX6B1 relieves hypoxia/reoxygenation injury of neonatal rat cardiomyocytes by regulating mitochondrial function

Tbx20 Induction Promotes Zebrafish Heart Regeneration by Inducing Cardiomyocyte Dedifferentiation and Endocardial Expansion

Four Dimensions of the Cardiac Myocyte Epigenome: from Fetal to Adult Heart

Contact Info

Product

Resources

About