In vitro differentiation of murine embryonic stem cells. New approaches to old problems.

Weiss, Mitchell J.; Orkin, Stuart H.

doi:10.1172/jci118454

Cited by 123 publications

(62 citation statements)

References 54 publications

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“…None of the other cells constituting the aortic wall presented a specific immunoreactivity for these antibodies. The staining with CD34, an antigen typically expressed in endothelial progenitor cells (Flamme and Risau, 1992;Weiss and Orkin, 1996), clearly showed that not only the lumen, but also the more peripheral/para-aortic cells, expressed this antigen. In a serial section of the same explant used for CD31 analysis, CD34 seems to be expressed by the para-aortic tissue (Fig.…”

Section: Characterization Of Embryonic Aortamentioning

confidence: 95%

Human Vasculogenesis Ex Vivo: Embryonal Aorta as a Tool for Isolation of Endothelial Cell Progenitors

Alessandri

Girelli

Taccagni

et al. 2001

Laboratory Investigation

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SUMMARY:Vasculogenesis, the de novo formation of new blood vessels from undifferentiated precursor cells or angioblasts, has been studied with experimental in vivo and ex vivo animal models, but its mechanism is poorly understood, particularly in humans. We used the aortic ring assay to investigate the angioforming capacity of aortic explants from 11-to 12-week-old human embryos. After being embedded in collagen gels, the aorta rings produced branching capillary-like structures formed by mesenchymal spindle cells that lined a capillary-like lumen and expressed markers of endothelial differentiation (CD31, CD34, von Willebrand factor [vWF], and fms-like tyrosine kinase-1 [Flk-1]/vascular endothelial growth factor receptor 2 [VEGFR2]). The cell linings of these structures showed ultrastructural evidence of endothelial differentiation. The neovascular proliferation occurred primarily in the outer aspects of aortic rings, thus suggesting that the new vessels mainly arose from immature endothelial precursor cells localized in the outer layer of the aortic stroma, ie, a process of vasculogenesis rather than angiogenesis. The undifferentiated mesenchymal cells (CD34ϩ/CD31Ϫ), isolated and cultured on collagen-fibronectin, differentiated into endothelial cells expressing CD31 and vWF. Furthermore, the CD34ϩ/CD31ϩ cells were capable of forming a network of capillary-like structures when cultured on Matrigel. This is the first reported study showing the ex vivo formation of human microvessels by vasculogenesis. Our findings indicate that the human embryonic aorta is a rich source of CD34ϩ/CD31Ϫ endothelial progenitor cells (angioblasts), and this information may prove valuable in studies of vascular regeneration and tissue bioengineering. (Lab Invest 2001, 81:875-885).

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Section: Characterization Of Embryonic Aortamentioning

confidence: 95%

Human Vasculogenesis Ex Vivo: Embryonal Aorta as a Tool for Isolation of Endothelial Cell Progenitors

Alessandri

Girelli

Taccagni

et al. 2001

Laboratory Investigation

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“…The pluripotency of ES cells is associated with an unfettered and plastic genome, accessible to transcriptional regulation and thus poised to differentiate into any cell type (Meshorer & Misteli, 2006). As pluirpotent cells are specified into tissue lineages they selectively activate specific subsets of genes (Eiges & Benvenisty, 2002;Loebel, Watson, De Young, & Tam, 2003;Weiss & Orkin, 1996). Regions of the genome that are not involved in the emerging cell lineage become silenced and thereafter remain inaccessible to transcriptional regulation (Eckfeldt, Mendenhall, & Verfaillie, 2005).…”

Section: Developmental Potency and Chromatin Reorganizationmentioning

confidence: 99%

Transdetermination: Drosophila imaginal disc cells exhibit stem cell-like potency

McClure

Schubiger

2007

The International Journal of Biochemistry & Cell Biology

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Drosophila imaginal discs, the primordia of the adult fly appendages, are an excellent system for studying developmental plasticity. Cells in the imaginal discs are determined for their disc-specific fate (wingness, legness) during embryogenesis. Disc cells maintain their determination during larval development, a time of extensive growth and proliferation. Only when prompted to regenerate do disc cells exhibit lability in their determined identity. Regeneration in the disc is mediated by a localized region of cell division, known as the regeneration blastema. Most regenerating disc cells strictly adhere to their disc-specific identity; some cells however, switch fate in a phenomenon known as transdetermination. Similar regeneration and transdetermination events can be induced in situ by misexpression of the signaling molecule wingless. Recent studies indicate that the plasticity of disc cells during regeneration is associated with high morphogen activity and the reorganization of chromatin structure. Here we provide both a historical perspective of imaginal disc transdetermination, as well as discuss recent findings on how imaginal disc cells acquire developmental plasticity and multipotency. We also highlight how an understanding of imaginal disc transdetermination can enhance an understanding of developmental potency exhibited by stem cells.

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“…These progenitor cells have consequently been considered to derive from a common precursor, putatively termed a hemangioblast. [102][103][104] Postnatal neovascularization has been previously considered to result exclusively from the proliferation, migration, and remodeling of fully differentiated endothelial cells derived from preexisting blood vessels, ie, angiogenesis (see Figure). 90,92,100 The formation of blood vessels from EPCs (ie, vasculogenesis) has been considered to be restricted to embryogenesis.…”

Section: Postnatal Vasculogenesismentioning

confidence: 99%

Estrogen and Angiogenesis

Losordo

Isner

2001

ATVB

302

194

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Abstract-Multiple lines of evidence suggest that estrogen directly modulates angiogenesis via effects on endothelial cells.Under physiological conditions, angiogenesis is routinely observed in the uterus in association with fluctuations in the levels of circulating estradiol and other sex steroids. In pathological circumstances, such as breast cancer, a clear association between estrogen, estrogen receptor expression by endothelial cells, angiogenic activity, and/or tumor invasiveness has been made. Studies performed in our laboratory have revealed that estradiol accelerates functional endothelial recovery after arterial injury. Despite these consistent observations, the mechanisms by which estrogen regulates angiogenesis under physiological and pathological circumstances have not been defined. Key Words: estrogen Ⅲ angiogenesis Ⅲ vasculogenesis Ⅲ endothelium Ⅲ endothelial progenitor cells I n adult organisms, angiogenesis is virtually absent under normal conditions, except in the female reproductive tract. This observation suggests the potential for sex steroids to influence neovascularization. Several other associations, including the predilection of certain diseases (such as Takayasu's arteritis and lupus, both of which involve endothelial cell proliferation) for premenopausal females, also imply the potential role of estrogen in angiogenesis. 1,2 The role of estradiol in uterine angiogenesis, mediated by at least 1 of the estrogen receptors, has been further suggested by findings in the estrogen receptor-␣ knockout mouse, in which angiogenesis is impaired, 3 and by the demonstration that estrogen receptor antagonists can inhibit angiogenesis. 4 The positive correlation between estrogen receptor expression, angiogenic activity, and breast tumor invasiveness also supports the angiogenic effect of estrogen mediated by the estrogen receptor(s). [5][6][7][8] Finally, some reports suggest that the antitumor effect of tamoxifen may in fact relate to an antiangiogenic action of this estrogen receptor agonist/antagonist. 9 Several additional lines of experimental evidence suggest that estrogen and other sex steroids play important roles in physiological and pathological angiogenesis. One of the first observations suggesting a hormonal influence on angiogenesis was an inhibitory effect on tumor vascularization by medroxyprogesterone. 10 Subsequent studies have indicated that the mechanism of this inhibition may relate to the regulation of thrombospondin-1, an angiogenesis inhibitor, by this hormone. 11 Angiogenesis has been noted to be a prognostic marker in breast cancer, 12 and inhibition of angiogenesis in these tumors has been effected by antiestrogens. 4 In addition, the estrogen metabolite 2-methoxyestradiol has been shown to be a potent antiangiogenic agent 13 mediated by actions on cytoskeletal structure 14 and by increasing endothelial cell apoptosis. 15,16 Vascular Endothelial Cell Proliferation and Migration Are Enhanced by EstradiolEstradiol induces endothelial proliferation and migration 17 mediated by t...

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In vitro differentiation of murine embryonic stem cells. New approaches to old problems.

Cited by 123 publications

References 54 publications

Human Vasculogenesis Ex Vivo: Embryonal Aorta as a Tool for Isolation of Endothelial Cell Progenitors

Human Vasculogenesis Ex Vivo: Embryonal Aorta as a Tool for Isolation of Endothelial Cell Progenitors

Transdetermination: Drosophila imaginal disc cells exhibit stem cell-like potency

Estrogen and Angiogenesis

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