Functional Cardiomyocytes Derived from Isl1 Cardiac Progenitors via Bmp4 Stimulation

Çağavı, Esra; Bartulos, Oscar; Suh, Carol Y.; Sun, Bingrong; Yue, Zhichao; Jiang, Zhengxin; Yue, Lixia; Qyang, Yibing

doi:10.1371/journal.pone.0110752

Cited by 24 publications

(21 citation statements)

References 43 publications

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“…Also unexpectedly, Isl1 that has been regarded as specific for the SHF was detected in most cDNA preparations in the EHF stage regardless of Tbx5 expression, although fewer Tbx5 + CPs in the EB stage expressed Isl1 compared to Nkx2-5 + CPs ( Fig 2A ). This evidence supports previous reports that Isl1 is detected among the FHF population [ 44 – 47 ]. As indicated by previous studies, Isl1 expression was down-regulated in differentiated cardiomyocytes at E8.5 ( Fig 2A and 2B ) [ 10 , 44 , 45 ].…”

Section: Resultssupporting

confidence: 93%

Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo

et al. 2015

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In the early vertebrate embryo, cardiac progenitor/precursor cells (CPs) give rise to cardiac structures. Better understanding their biological character is critical to understand the heart development and to apply CPs for the clinical arena. However, our knowledge remains incomplete. With the use of single-cell expression profiling, we have now revealed rapid and dynamic changes in gene expression profiles of the embryonic CPs during the early phase after their segregation from the cardiac mesoderm. Progressively, the nascent mesodermal gene Mesp1 terminated, and Nkx2-5 +/Tbx5 + population rapidly replaced the Tbx5 low+ population as the expression of the cardiac genes Tbx5 and Nkx2-5 increased. At the Early Headfold stage, Tbx5-expressing CPs gradually showed a unique molecular signature with signs of cardiomyocyte differentiation. Lineage-tracing revealed a developmentally distinct characteristic of this population. They underwent progressive differentiation only towards the cardiomyocyte lineage corresponding to the first heart field rather than being maintained as a progenitor pool. More importantly, Tbx5 likely plays an important role in a transcriptional network to regulate the distinct character of the FHF via a positive feedback loop to activate the robust expression of Tbx5 in CPs. These data expands our knowledge on the behavior of CPs during the early phase of cardiac development, subsequently providing a platform for further study.

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Section: Resultssupporting

confidence: 93%

Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo

et al. 2015

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“…Following signalling activation via BMP type-1 or type-2 receptors, phosphorylated receptor-regulated SMADs form heterodimeric complexes with the common mediator SMAD4 and translocate to the nucleus to regulate gene expression. In the heart, BMP pathways play a pivotal role in the embryogenesis of the left ventricular chamber 33 , the differentiation of cardiac progenitor cells into functional cardiomyocytes 34 , maintenance of the balance between left ventricular growth and apoptosis 35 , initiation of fibrosis 35 , and Ca 2+ channel remodelling 36 . In analogy with the cardiac findings, previous studies demonstrated that BMP and TGF-β2 signalling pathways are also active in the eye 26 , 37 – 39 .…”

Section: Discussionmentioning

confidence: 99%

Inactive matrix Gla protein is a novel circulating biomarker predicting retinal arteriolar narrowing in humans

Wei

Huang

Zhang

et al. 2018

Sci Rep

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Active matrix Gla protein (MGP), a potent inhibitor of calcification in large arteries, protects against macrovascular complications. Recent studies suggested that active MGP helps maintaining the integrity of the renal and myocardial microcirculation, but its role in preserving the retinal microcirculation remains unknown. In 935 randomly recruited Flemish participants (mean age, 40.9 years; 50.3% women), we measured plasma desphospho-uncarboxylated MGP (dp–ucMGP), a marker of poor vitamin K status using an ELISA-based assay at baseline (1996–2010) and retinal microvascular diameters using IVAN software (Vasculomatic ala Nicola, version 1.1) including the central retinal arteriolar (CRAE) and venular (CRVE) equivalent and the arteriole-to-venule ratio (AVR) at follow-up (2008–2015). CRAE (P = 0.005) and AVR (P = 0.080) at follow-up decreased across tertiles of the dp–ucMGP distribution. In unadjusted models, for a doubling of dp–ucMGP at baseline, CRAE and AVR at follow-up respectively decreased by 1.40 µm (95% confidence interval [CI], 0.32 to 2.48; P = 0.011) and 0.006 (CI, 0.001 to 0.011; P = 0.016). In multivariable-adjusted models accounting for sex, baseline characteristics and follow-up duration, these estimates were −1.03 µm (CI, −1.96 to −0.11; P = 0.028) and −0.007 (CI, −0.011 to −0.002; P = 0.007). Additional adjustment for changes from baseline to follow-up in major baseline characteristics yielded as estimates −0.91 µm (CI, −1.82 to −0.01; P = 0.048) and −0.006 (95% CI, −0.011 to −0.001; P = 0.014), respectively. Circulating inactive dp–ucMGP is a long-term predictor of smaller retinal arteriolar diameter in the general population. Our observations highlight the possibility that vitamin K supplementation might promote retinal health.

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“…In vivo activation of β-catenin has been shown to promote the expansion of Isl-1 + CSCs through the regulation of fibroblast growth factor (FGF) signaling, suggesting that the Wnt/beta-catenin signaling pathway regulates renewal of Isl-1 + progenitors (Cohen et al, 2007;Qyang et al, 2007). Functional cardiomyocytes can be differentiated from Isl-1 + CSC population through bone morphogenic protein 4 (BMP4) signal activation (Cagavi et al, 2014). Another study showed that Notch1 signaling also regulates self-renewal, maintenance of cardiac progenitors, and the requirement for Notch1 activity in cardiac differentiation (Kwon et al, 2009).…”

Section: Isl-1 + Cellsmentioning

confidence: 99%

The heart of the matter: cardiac stem cells

Çağavı¹,

Koç²,

Goktas³

2016

Turk J Biol

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Cardiovascular diseases are the primary cause of death in the world. Pharmacological and surgical approaches are the main treatment options for heart disease; however, heart transplantation may be the only option for advanced heart failure patients despite its limited nature. Recent advances enabled stem cell-based therapies to become a promising treatment approach for injured or weakened cardiac tissue. With the identification of resident and heart-specific stem cells in early 2000, new avenues of research have been opened to understand heart development, disease, and regeneration. In this review article, different cardiac stem cell subpopulations are classified and defined based on the expression of various characteristic surface or intracellular proteins, including, but not limited to, C-kit, Sca-1, Isl-1, Nkx2.5, HCN4, SIRPA, Flt-1, and KDR. Understanding cardiac stem cell biology, self-renewal, and differentiation mechanisms holds great promise for directing these processes and utilizing these cells to repair or even build new hearts.

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Functional Cardiomyocytes Derived from Isl1 Cardiac Progenitors via Bmp4 Stimulation

Cited by 24 publications

References 43 publications

Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo

Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo

Inactive matrix Gla protein is a novel circulating biomarker predicting retinal arteriolar narrowing in humans

The heart of the matter: cardiac stem cells

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