Fibroblast growth factor 2 up regulates telomerase activity in neural precursor cells

Haı̈k, Stéphane; Gauthier, Laurent; Granotier, Christine; Peyrin, Jean‐Michel; Lages, Celine S.; Dormont, Dominique; Boussin, François D.

doi:10.1038/sj.onc.1203596

Cited by 60 publications

(46 citation statements)

References 69 publications

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“…Basically, given the difference of telomere and telomerase activity in human and mouse cells, the telomere and telomerase status in stem cell populations is different between humans and mice (Harrington, 2004). The level of telomerase is low in the majority of human stem cells, whereas it is upregulated in cells that undergo rapid expansion, such as committed haematopoietic progenitor cells, activated lymphocytes, or keratinocytes, even within tissues with a low cell turnover such as the brain (Haik et al, 2000; Figure 1). …”

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confidence: 99%

Telomere and telomerase in stem cells

2007

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Telomeres, guanine-rich tandem DNA repeats of the chromosomal end, provide chromosomal stability, and cellular replication causes their loss. In somatic cells, the activity of telomerase, a reverse transcriptase that can elongate telomeric repeats, is usually diminished after birth so that the telomere length is gradually shortened with cell divisions, and triggers cellular senescence. In embryonic stem cells, telomerase is activated and maintains telomere length and cellular immortality; however, the level of telomerase activity is low or absent in the majority of stem cells regardless of their proliferative capacity. Thus, even in stem cells, except for embryonal stem cells and cancer stem cells, telomere shortening occurs during replicative ageing, possibly at a slower rate than that in normal somatic cells. Recently, the importance of telomere maintenance in human stem cells has been highlighted by studies on dyskeratosis congenital, which is a genetic disorder in the human telomerase component. The regulation of telomere length and telomerase activity is a complex and dynamic process that is tightly linked to cell cycle regulation in human stem cells. Here we review the role of telomeres and telomerase in the function and capacity of the human stem cells.

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confidence: 99%

Telomere and telomerase in stem cells

2007

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“…Adherence to plastic support induces the differentiation of primary telencephalic cells isolated from C57BL/6 mouse E15 embryos (Haik et al, 2000). Therefore, to enrich cultures in neural progenitors, cells were cultured in a defined medium supplemented with fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF).…”

Section: Neurosphere Cultures Of Primary Neural Progenitorsmentioning

confidence: 99%

Involvement of p53 and Fas/CD95 in murine neural progenitor cell response to ionizing irradiation

et al. 2004

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We investigated the role of tumor suppressor p53 and Fas (CD95/APO-1), a member of the tumor necrosis factor receptor family, in neural progenitors response to cirradiation exposure. Telencephalic cells were obtained from wild-type C57Bl/6, or p53À/À or fasÀ/À, 15-dayold mouse embryos. They were cultured in conditions allowing neural progenitors to form proliferating clusters (neurospheres). A 2 Gy c-irradiation induced a G1 cell cycle arrest and triggered apoptosis in wild-type neural progenitor cultures in correlation with an enhanced expression of p53 and of its downstream target p21 WAF1 , both of them acquiring a nuclear localization. These effects did not occur in p53À/À neural progenitors demonstrating the central role played by p53 in their response to ionizing radiation. Furthermore, the monoclonal antibody Jo2 directed against Fas induced apoptosis of wild type but not of fasÀ/À neural progenitors, indicating the existence of a functional Fas signaling pathway in neural progenitors. Ionizing radiation induced an increase of Fas membrane expression related to a p53-dependent increase of fas mRNA expression in wild-type neural progenitors. Moreover, fasÀ/À neural progenitors exhibited delayed radiation-induced apoptosis compared to wild-type cells. Therefore, these findings establish a role for Fas/CD95 related to p53 in the response of neural progenitors to c-radiation exposure. Similar mechanisms could be triggered in neural progenitors in case of different stresses during brain development or in the course of various diseases affecting the adult brain.

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“…Assays have been performed twice in independent experiments using a constant amount of 0.1 µg of lysates, for each sample that permits obtaining DO values in the linear range of the assay (Haik et al, 2000). Each sample was tested along with a heat inactivated (65˚C for 10 min) or RNase-treated aliquot.…”

Section: Telomerase Assaymentioning

confidence: 99%

Telomerase activation cooperates with inactivation of p16 in early head and neck tumorigenesis

et al. 2001

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Summary Alteration of the p16/pRb pathway may cooperate with telomerase activation during cellular immortalization and tumour progression. We studied p16 expression status by immunohistochemistry and telomerase activity using the TRAP assay in 21 premalignant lesions of the head and neck epithelium as well as 27 squamous-cell carcinomas. We also examined expression of other components of the pathway (cyclin D1 and pRb) as well as presence of human papillomavirus genomes which can target these molecules. 4 of 9 mild dysplastic lesions (44%), 8 of 12 moderate/severe dysplastic lesions (67%), and 25 of 27 squamous-cell carcinomas (92%) demonstrated high telomerase activity (P = 0.009). There was a parallel increase with severity of lesions for the trend in proportions of cases demonstrating p16 inactivation or cyclin D1 overexpression (P = 0.02 and P = 0.01, respectively). For Ki67, a marker of cell proliferation, this trend was not significant (P = 0.08). Human papillomavirus infection was only found in 4 cases among the 48 samples tested (8.3%). In conclusion, progression of disease is accompanied by a parallel and continuous increase in telomerase activity and alterations in cell cycle regulators (p16, cyclin D1), as proposed by in vitro models. of this pathway (i.e. pRb and cyclin D1). Moreover and since the p16/pRb pathway can also be targeted by the E7 gene product of oncogenic human papillomaviruses (HPV) (Jones and Munger, 1996), we have also performed a PCR-detection of HPV genome in our samples.

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Fibroblast growth factor 2 up regulates telomerase activity in neural precursor cells

Cited by 60 publications

References 69 publications

Telomere and telomerase in stem cells

Telomere and telomerase in stem cells

Involvement of p53 and Fas/CD95 in murine neural progenitor cell response to ionizing irradiation

Telomerase activation cooperates with inactivation of p16 in early head and neck tumorigenesis

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