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

Tang, Yan; Chen, Zhongyan; Hong, Yazhen; Wu, Qiang; Lin, Hanqing; Chen, Charlie Degui; Yang, Huang‐Tian

doi:10.1038/aps.2014.40

Cited by 9 publications

(7 citation statements)

References 45 publications

(57 reference statements)

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“…mESC-derived T-GFP + mesodermal cells [26] at differentiation day 3 and FLK1 + /CXCR4 + CPCs [23] at differentiation day 5 were isolated from corresponding T-GFP − and FLK1 − /CXCR4 − populations by FACS (Supplemental Figure S1A–C) as previously described [27]. The enriched T-GFP + and FLK1 + /CXCR4 + fractions were confirmed by RT-PCR analysis of mesodermal marker T and cardiac progenitor marker Nkx2.5 , Isl1 , Tbx5 , and Mef2c .…”

Section: Resultsmentioning

confidence: 99%

“…To identify miRNAs that might be involved in the cardiac lineage commitment, we screened miRNA expression profiles at the mesodermal and cardiac progenitor stages, which are essential for the cardiac lineage commitment [ 25 ]. mESC-derived T-GFP + mesodermal cells [ 26 ] at differentiation day 3 and FLK1 + /CXCR4 + CPCs [ 23 ] at differentiation day 5 were isolated from corresponding T-GFP − and FLK1 − /CXCR4 − populations by FACS (Supplemental Figure S1A–C) as previously described [ 27 ]. The enriched T-GFP + and FLK1 + /CXCR4 + fractions were confirmed by RT-PCR analysis of mesodermal marker T and cardiac progenitor marker Nkx2.5 , Isl1 , Tbx5 , and Mef2c .…”

Section: Resultsmentioning

confidence: 99%

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miR-142-3p Contributes to Early Cardiac Fate Decision of Embryonic Stem Cells

Chen

Cao

et al. 2017

Stem Cells International

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MicroRNAs (miRNAs) play important roles in cell fate decisions. However, the miRNAs and their targets involved in the regulation of cardiac lineage specification are largely unexplored. Here, we report novel functions of miR-142-3p in the regulation of cardiomyocyte differentiation from mouse embryonic stem cells (mESCs). With a miRNA array screen, we identified a number of miRNAs significantly changed during mESC differentiation into the mesodermal and cardiac progenitor cells, and miR-142-3p was one among the markedly downregulated miRNAs. Ectopic expression and inhibition of miR-142-3p did not alter the characteristics of undifferentiated ESCs, whereas ectopic expression of miR-142-3p impaired cardiomyocyte formation. In addition, ectopic expression of miR-142-3p inhibited the expression of a cardiac mesodermal marker gene Mesp1 and downstream cardiac transcription factors Nkx2.5, Tbx5, and Mef2c but not the expression of three germ layer-specific genes. We further demonstrated that miR-142-3p targeted the 3′-untranslated region of Mef2c. These results reveal miR-142-3p as an important regulator of early cardiomyocyte differentiation. Our findings provide new knowledge for further understanding of roles and mechanisms of miRNAs as critical regulators of cardiomyocyte differentiation.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

miR-142-3p Contributes to Early Cardiac Fate Decision of Embryonic Stem Cells

Chen

Cao

et al. 2017

Stem Cells International

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“…Tripsinized undifferentiated or differentiating cells were prepared as described , and incubated with antibodies to FLK‐1 (Cat No. 560070, BD Biosciences, Bedford, MA, 1:200), NESTIN (Cat No.…”

Section: Methodsmentioning

confidence: 99%

“…Total RNA was isolated using Trizol (Invitrogen) and analyzed by reverse transcription‐PCR (RT‐PCR) and quantitative RT‐PCR (qRT‐PCR) as described . The transcripts of m28s and gapdh were used for internal controls.…”

Section: Methodsmentioning

confidence: 99%

Plant Homeo Domain Finger Protein 8 Regulates Mesodermal and Cardiac Differentiation of Embryonic Stem Cells Through Mediating the Histone Demethylation of pmaip1

et al. 2016

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Histone demethylases have emerged as key regulators of biological processes. The H3K9me2 demethylase plant homeo domain finger protein 8(PHF8), for example, is involved in neuronal differentiation, but its potential function in the differentiation of embryonic stem cells (ESCs) to cardiomyocytes is poorly understood. Here, we explored the role of PHF8 during mesodermal and cardiac lineage commitment of mouse ESCs (mESCs). Using a phf8 knockout (ph8 -/Y ) model, we found that deletion of phf8 in ESCs did not affect self-renewal, proliferation or early ectodermal/endodermal differentiation, but it did promote the mesodermal lineage commitment with the enhanced cardiomyocyte differentiation. The effects were accompanied by a reduction in apoptosis through a caspase 3-independent pathway during early ESC differentiation, without significant differences between differentiating wide-type (ph8 1/Y ) and ph8 -/Y ESCs in cell cycle progression or proliferation. Functionally, PHF8 promoted the loss of a repressive mark H3K9me2 from the transcription start site of a proapoptotic gene pmaip1 and activated its transcription. Furthermore, knockdown of pmaip1 mimicked the phenotype of ph8 -/Y by showing the decreased apoptosis during early differentiation of ESCs and promoted mesodermal and cardiac commitment, while overexpression of pmaip1 or phf8 rescued the phenotype of ph8 -/Y ESCs by increasing the apoptosis and weakening the mesodermal and cardiac differentiation. These results reveal that the histone demethylase PHF8 regulates mesodermal lineage and cell fate decisions in differentiating mESCs through epigenetic control of the gene critical to programmed cell death pathways. STEM CELLS 2016;34:1527-1540 SIGNIFICANCE STATEMENTEmbryonic stem cells (ESCs) have the unique ability to differentiate into derivatives of all three germ layers both in vitro and in vivo. Thus, ESCs provide a unique model for the study of early embryonic development. We report here previously unrecognized effects of histone demethylase plant homeo domain finger protein 8 (PHF8) on mesodermal and early cardiac differentiation. This effect is resulted from the regulation of PHF8 on apoptosis through activating the transcription of pro-apoptotic gene pmaip1. These findings extend the knowledge in understanding of the epigenetic modification in apoptosis during ESC differentiation and of the link between apoptosis and cell lineage decision as well as cardiogenesis.

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“…Many histone demethylases have been studied in connection with the development of hypertrophy and other cardiovascular diseases. However, the lysine histone demethylase oxygenase (JMJD/KDM) family probably has a greater impact on such diseases [ 15 , 16 ]. Lysine-specific demethylase 4A (JMJD2A/KDM4A) was the first tridemethylase discovered [ 17 ], with the capacity to demethylate the H3K9m 3 and H3K36m 3 , which can increase gene expression [ 17 – 19 ].…”

Section: Introductionmentioning

confidence: 99%

Role of Histone Demethylases in Cardiomyocytes Induced to Hypertrophy

Rosales

Carulla

García

et al. 2016

BioMed Research International

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Epigenetic changes induced by histone demethylases play an important role in differentiation and pathological changes in cardiac cells. However, the role of the jumonji family of demethylases in the development of cardiac hypertrophy remains elusive. In this study, the presence of different histone demethylases in cardiac cells was evaluated after hypertrophy was induced with neurohormones. A cell line from rat cardiomyocytes was used as a biological model. The phenotypic profiles of the cells, as well as the expression of histone demethylases, were studied through immunofluorescence, transient transfection, western blot, and qRT-PCR analysis after inducing hypertrophy by angiotensin II and endothelin-1. An increase in fetal gene expression (ANP, BNP, and β-MHC) was observed in cardiomyocytes after treatment with angiotensin II and endothelin-1. A significant increase in JMJD2A expression, but not in UTX or JMJD2C expression, was observed. When JMJD2A was overexpressed in cardiomyocytes through transient transfection, the effect of neurohormones on fetal cardiac gene expression was increased. We conclude that JMJD2A plays a principal role in the regulation of fetal cardiac genes, which increase in expression during the pathological hypertrophic process.

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

Cited by 9 publications

References 45 publications

miR-142-3p Contributes to Early Cardiac Fate Decision of Embryonic Stem Cells

miR-142-3p Contributes to Early Cardiac Fate Decision of Embryonic Stem Cells

Plant Homeo Domain Finger Protein 8 Regulates Mesodermal and Cardiac Differentiation of Embryonic Stem Cells Through Mediating the Histone Demethylation of pmaip1

Role of Histone Demethylases in Cardiomyocytes Induced to Hypertrophy

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