Multipotent Embryonic Isl1+ Progenitor Cells Lead to Cardiac, Smooth Muscle, and Endothelial Cell Diversification

Moretti, Alessandra; Caron, Leslie; Nakano, Atsushi; Lam, Jason T.; Bernshausen, Alexandra; Chen, Yinhong; Qyang, Yibing; Bu, Lei; Sasaki, Mika; Martı́n-Puig, Silvia; Sun, Yunfu; Evans, Sylvia M.; Laugwitz, Karl‐Ludwig; Chien, Kenneth R.

doi:10.1016/j.cell.2006.10.029

Cited by 967 publications

(957 citation statements)

References 49 publications

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“…Eomes overexpression also promoted the appearance of endothelial cells (expressing VE-cadherin and CD31; Fig 1D,E,J) and smooth muscle cells (expressing smooth muscle actin; Fig 1F,G,K and supplementary Fig S2B online). Altogether, the three types of cells derived from multipotent cardiovascular progenitors (MCPs) [27,[35][36][37] were massively increased following Eomes expression in DDM, although we cannot rule out that some endothelial and smooth muscle cells could also derive from other progenitors (such as the hemangioblasts [38] that could also be induced following Eomes expression). We and others have recently demonstrated that a combination of monoclonal antibodies (Flk1/Pdgfra) can be used to isolate the earliest Mesp1 expressing MCPs arising during ESC differentiation [16,27].…”

Section: Results and Discussion Eomes Promotes Cardiogenesis In Escmentioning

confidence: 99%

Eomesodermin induces Mesp1 expression and cardiac differentiation from embryonic stem cells in the absence of Activin

et al. 2012

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The transcription factor Eomesodermin (Eomes) is involved in early embryonic patterning, but the range of cell fates that it controls as well as its mechanisms of action remain unclear. Here we show that transient expression of Eomes promotes cardiovascular fate during embryonic stem cell differentiation. Eomes also rapidly induces the expression of Mesp1, a key regulator of cardiovascular differentiation, and directly binds to regulatory sequences of Mesp1. Eomes effects are strikingly modulated by Activin signalling: high levels of Activin inhibit the promotion of cardiac mesoderm by Eomes, while they enhance Eomes-dependent endodermal specification. These results place Eomes upstream of the Mesp1-dependent programme of cardiogenesis, and at the intersection of mesodermal and endodermal specification, depending on the levels of Activin/Nodal signalling.

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Section: Results and Discussion Eomes Promotes Cardiogenesis In Escmentioning

confidence: 99%

Eomesodermin induces Mesp1 expression and cardiac differentiation from embryonic stem cells in the absence of Activin

et al. 2012

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“…Thus, by applying the appropriate concentration of SmartFlare TM Probes, which may vary in different cell types, the vast majority of a given target population should be labeled. For example, a cardiac precursor population positive for Islet1 has recently been described [35][36][37]. This rare population could be enriched by FACS sorting from iPS cultures using an Islet1-specific SmartFlare TM Probe.…”

Section: Live Screening Of Successfully Reprogrammed Murine Ttfs To Imentioning

confidence: 99%

Live Fluorescent RNA-Based Detection of Pluripotency Gene Expression in Embryonic and Induced Pluripotent Stem Cells of Different Species

Lahm

Doppler²,

Dreßen³

et al. 2015

Stem Cells

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The generation of induced pluripotent stem (iPS) cells has successfully been achieved in many species. However, the identification of truly reprogrammed iPS cells still remains laborious and the detection of pluripotency markers requires fixation of cells in most cases. Here, we report an approach with nanoparticles carrying Cy3-labeled sense oligonucleotide reporter strands coupled to gold-particles. These molecules are directly added to cultured cells without any manipulation and gene expression is evaluated microscopically after overnight incubation. To simultaneously detect gene expression in different species, probe sequences were chosen according to interspecies homology. With a common target-specific probe we could successfully demonstrate expression of the GAPDH house-keeping gene in somatic cells and expression of the pluripotency markers NANOG and GDF3 in embryonic stem cells and iPS cells of murine, human, and porcine origin. The population of target gene positive cells could be purified by fluorescence-activated cell sorting. After lentiviral transduction of murine tail-tip fibroblasts Nanog-specific probes identified truly reprogrammed murine iPS cells in situ during development based on their Cy3-fluorescence. The intensity of Nanog-specific fluorescence correlated positively with an increased capacity of individual clones to differentiate into cells of all three germ layers. Our approach offers a universal tool to detect intracellular gene expression directly in live cells of any desired origin without the need for manipulation, thus allowing conservation of the genetic background of the target cell. Furthermore, it represents an easy, scalable method for efficient screening of pluripotency which is highly desirable during high-throughput cell reprogramming and after genomic editing of pluripotent stem cells. STEM CELLS 2015;33:392-402

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“…22 Laugwitz et al 23 demonstrated the presence of an Isl-1 + population of cardiac stem cells in the postnatal mouse, rat, and human heart, most prominently in the outflow tract and right atrium. Further studies showed that Isl-1 marks a population of multipotent cardiac stem cells contributing to smooth muscle, endothelial, and pacemaker cell lineages in the embryonic and postnatal heart 24,25 and implicate Isl-1 + Nkx2.5 + Flk-1 + cells as the most primitive cardiac stem cells. No compelling evidence for an Isl-1 + population in the adult heart has been presented.…”

Section: Isl-1 + Cardiac Stem Cellsmentioning

confidence: 99%

Stem cells in the heart: What's the buzz all about?—Part 1: Preclinical considerations

et al. 2008

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New approaches for cardiac repair have been enabled by the discovery that the heart contains its own reservoir of stem cells. These cells are positive for various stem/progenitor cell markers, are selfrenewing, and exhibit multilineage differentiation potential. Recently we developed a method for ex vivo expansion of cardiac-derived stem cells from human myocardial biopsies with a view to subsequent autologous transplantation for myocardial regeneration. Here we review the state of the cardiac stem cell field and our own work on cardiosphere-derived stem cells from human hearts. The first of this two-part review outlines emerging preclinical data on the application of cardiac stem cells. Part 2 continues with a discussion of other stem cell sources with clinical potential, a summary of the critical issues surrounding stem cell therapy (with an emphasis on the crucial issue of how cell transplantation may influence arrhythmias), our perception of clinical stem cell trials to date, and the issues facing the clinical application of cardiac stem cells.

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Multipotent Embryonic Isl1+ Progenitor Cells Lead to Cardiac, Smooth Muscle, and Endothelial Cell Diversification

Cited by 967 publications

References 49 publications

Eomesodermin induces Mesp1 expression and cardiac differentiation from embryonic stem cells in the absence of Activin

Eomesodermin induces Mesp1 expression and cardiac differentiation from embryonic stem cells in the absence of Activin

Live Fluorescent RNA-Based Detection of Pluripotency Gene Expression in Embryonic and Induced Pluripotent Stem Cells of Different Species

Stem cells in the heart: What's the buzz all about?—Part 1: Preclinical considerations

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