Jmjd3 Controls Mesodermal and Cardiovascular Differentiation of Embryonic Stem Cells

Ohtani, Kisho; Zhao, Cong; Dobreva, Gergana; Manavski, Yosif; Kluge, Britta; Braun, Thomas; Rieger, Michael A.; Zeiher, Andreas M.; Dimmeler, Stefanie

doi:10.1161/circresaha.113.302035

Cited by 79 publications

(94 citation statements)

References 27 publications

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“…We found that the Jmjd3 expression levels increased significantly during cardiac differentiation, suggesting that Jmjd3 may play an important role in this process. This result is consistent with the recent finding that Jmjd3 functions in control- [19] . Jmjd3 also has demethylase-independent functions: Miller et al [35] reported that Jmjd3 mediates a functional interaction between the lineage-defining T-box transcription factor family member and its target genes.…”

Section: Discussionsupporting

confidence: 94%

“…After differentiation, most of the marks are removed [15] , implying that the enzymes responsible for demethylation may play a role in ESC www.nature.com/aps Tang Y et al Acta Pharmacologica Sinica npg differentiation. It has been shown that histone lysine demethylases (KDMs) play an important role in the self-renewal of ESCs [16][17][18] and in cardiac differentiation [19,20] . However, the specific KDMs that control the differentiation of ESCs are largely unknown.…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies have revealed that the Kdm6 family members Utx and Jmjd3 play important roles in the cardiovascular lineage specification of ESCs through different mechanisms. Jmjd3 reduces the H3K27me3 marks at the Brachyury promoter and facilitates the recruitment of b-catenin, which is critical for Wnt signal-induced mesoderm differentiation and cardiovascular lineage commitment [19] . Unlike Jmjd3, Utx controls mesoderm differentiation and Brachyury expression independent of H3K27 demethylase activity [22] ; Utx also associates with core cardiac transcription factors and demethylates H3K27 residues in cardiac-specific genes [20] .…”

Section: Introductionmentioning

confidence: 99%

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Expression profiles of histone lysine demethylases during cardiomyocyte differentiation of mouse embryonic stem cells

et al. 2014

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Aim: Histone lysine demethylases (KDMs) control the lineage commitments of stem cells. However, the KDMs involved in the determination of the cardiomyogenic lineage are not fully defined. The aim of this study was to investigate the expression profiles of KDMs during the cardiac differentiation of mouse embryonic stem cells (mESCs). Methods: An in vitro cardiac differentiation system of mESCs with Brachyury (a mesodermal specific marker) and Flk-1 + /Cxcr4 + (dual cell surface biomarkers) selection was used. The expression profiles of KDMs during differentiation were analyzed using Q-PCR. To understand the contributions of KDMs to cardiomyogenesis, the mESCs on differentiation d 3.5 were sorted by FACS into Brachyury + cells and Brachyury -cells, and mESCs on d 5.5 were sorted into Flk-1 + /Cxcr4 + and Flk-1 -/Cxcr4 -cells. Results: mESCs were differentiated into spontaneously beating cardiomyocytes that were visible in embryoid bodies (EBs) on d 7. On d 12-14, all EBs developed spontaneously beating cardiomyocytes. Among the 16 KDMs examined, the expression levels of Phf8, Jarid1a, Jhdm1d, Utx, and Jmjd3 were increased by nearly 2-6-fold on d 14 compared with those on d 0. Brachyury + cells showed higher expression levels of Jmjd3, Jmjd2a and Jhdm1d than Brachyury -cells. A higher level of Jmjd3 was detected in Flk-1 + /Cxcr4 + cells, whereas the level of Jmjd2c was lower in both Brachyury + cells and Flk-1 + /Cxcr4 + cells. Conclusion: KDMs may play important roles during cardiomyogenesis of mESCs. Our results provide a clue for further exploring the roles of KDMs in the cardiac lineage commitment of mESCs and the potential interference of cardiomyogenesis.

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Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Expression profiles of histone lysine demethylases during cardiomyocyte differentiation of mouse embryonic stem cells

et al. 2014

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“…KDM6B is 0.42 Mb away from the top SNP (ALGA0121951) at the genome-wide significant locus on SSC12. This gene plays a critical role in guiding the expression of T-box gene family in embryonic stem cell differentiation [31]. T-box3 , a member of the T-box gene family, has been reported to influence the development of mammary gland placodes via interacting with Wnt family member 10 ( Wnt10 ), lymphoid enhancer binding factor 1 ( lef-1 ), and fibroblast growth factor 10 ( Fgf10 ) [32–34].…”

Section: Discussionmentioning

confidence: 99%

Identification of loci affecting teat number by genome-wide association studies on three pig populations

Tang

Zhang

Yang

et al. 2016

Asian-Australas J Anim Sci

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ObjectiveThree genome-wide association studies (GWAS) and a meta-analysis of GWAS were conducted to explore the genetic mechanisms underlying variation in pig teat number.MethodsWe performed three GWAS and a meta-analysis for teat number on three pig populations, including a White Duroc×Erhualian F2 resource population (n = 1,743), a Chinese Erhualian pig population (n = 320) and a Chinese Sutai pig population (n = 383).ResultsWe detected 24 single nucleotide polymorphisms (SNPs) that surpassed the genome-wide significant level on Sus Scrofa chromosomes (SSC) 1, 7, and 12 in the F2 resource population, corresponding to four loci for pig teat number. We highlighted vertnin (VRTN) and lysine demethylase 6B (KDM6B) as two interesting candidate genes at the loci on SSC7 and SSC12. No significant associated SNPs were identified in the meta-analysis of GWAS.ConclusionThe results verified the complex genetic architecture of pig teat number. The causative variants for teat number may be different in the three populations

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“…Similarly, Jmjd3 knockout ESCs fail to differentiate into mesoderm and cardiac lineages [94]. Global genetic deletion of Utx results in embryonic lethality by E13.5 with developmental abnormalities in cardiac chamber formation [92,93].…”

Section: Histone Methyltrasnferases Are Required For Cardiomyocyte Prmentioning

confidence: 99%

Resetting the epigenome for heart regeneration.

Quaife-Ryan

Sim

Porrello

et al. 2016

Seminars in Cell & Developmental Biology

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In contrast to adults, recent evidence suggests that neonatal mice are able to regenerate following cardiac injury. This regenerative capacity is reliant on robust induction of cardiomyocyte proliferation, which is required for faithful regeneration of the heart following injury. However, cardiac regenerative potential is lost as cardiomyocytes mature and permanently withdraw from the cell cycle shortly after birth. Recently, a handful of factors responsible for the regenerative disparity between the adult and neonatal heart have been identified, but the proliferative response of adult cardiomyoctes following modulation of these factors rarely reaches neonatal levels. The inefficient re-induction of proliferation in adult cardiomyocytes may be due to the epigenetic landscape, which drastically changes during cardiac development and maturation. In this review, we provide an overview of the role of epigenetic modifiers in developmental processes related to cardiac regeneration. We propose an epigentic framework for heart regeneration whereby adult cardiomyocyte identity requires resetting to a neonatal-like state to facilitate cell cycle re-entry and regeneration following cardiac injury.

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Jmjd3 Controls Mesodermal and Cardiovascular Differentiation of Embryonic Stem Cells

Cited by 79 publications

References 27 publications

Expression profiles of histone lysine demethylases during cardiomyocyte differentiation of mouse embryonic stem cells

Expression profiles of histone lysine demethylases during cardiomyocyte differentiation of mouse embryonic stem cells

Identification of loci affecting teat number by genome-wide association studies on three pig populations

Resetting the epigenome for heart regeneration.

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