TRAPping telomerase within the intestinal stem cell niche.

Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
The EMBO Journal (Impact Factor: 10.75). 03/2011; 30(6):986-7. DOI: 10.1038/emboj.2011.51
Source: PubMed
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    ABSTRACT: Telomerase expression in humans is restricted to different populations of stem and progenitor cells, being silenced in most somatic tissues. Efficient telomere homeostasis is essential for embryonic and adult stem cell function and therefore essential for tissue homeostasis throughout organismal life. Accordingly, the mutations in telomerase culminate in reduced stem cell function both in vivo and in vitro and have been associated with tissue dysfunction in human patients. Despite the importance of telomerase for stem cell biology, the mechanisms behind telomerase regulation during development are still poorly understood, mostly due to difficulties in acquiring and maintaining pluripotent stem cell populations in culture. In this chapter, we will analyze recent developments in this field, including the importance of efficient telomere homeostasis in different stem cell types and the role of telomerase in different techniques used for cellular reprogramming.
    Progress in molecular biology and translational science 01/2014; 125C:67-88. · 3.11 Impact Factor
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    ABSTRACT: Here, we report a novel type of signal-on dual-potential electrochemiluminescence (ECL) approach for telomerase detection based on bifunctionalized luminol-Au nanoparticles (L-Au NPs). In this approach, CdS nanocrystals (NCs) were firstly coated on glassy carbon electrode, and then thiol modified telomerase primer was attached on CdS NCs via Cd-S bond. In the presence of telomerase and dNTPs, the primer could be extended. Telomerase primer would hybridize with its complementary DNA and the extended part would hybridize with the capture DNA which was tagged with L-Au NPs. In the presence of coreactant H2O2, the L-Au NPs which could not only enhance the ECL intensity of CdS NCs at -1.25 V (vs SCE) induced by surface plasmon resonance (SPR) of Au NPs, but also produce a new ECL signal at +0.45 V (vs SCE) resulted from luminol in L-Au NPs. Both signals at two potentials increased with the increase of telomerase concentration. This method could be used to detect the telomerase from 100 to 9 000 HL-60 cells and investigate the apoptosis of tumor cells. The ratio of the two signal-increments (△ECLLuminol/△ECLCdS NCs) which showed a high consistency value for different number of cells could be used to verify the reliability of tests. This dual-potential ECL strategy showed great promise in avoiding false positive or negative results in bioanalysis.
    Analytical Chemistry 03/2014; · 5.83 Impact Factor
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    ABSTRACT: Mass spectrometry with stable isotope labels has been seminal in discovering the dynamic state of living matter, but is limited to bulk tissues or cells. We developed multi-isotope imaging mass spectrometry (MIMS) that allowed us to view and measure stable isotope incorporation with submicrometre resolution. Here we apply MIMS to diverse organisms, including Drosophila, mice and humans. We test the 'immortal strand hypothesis', which predicts that during asymmetric stem cell division chromosomes containing older template DNA are segregated to the daughter destined to remain a stem cell, thus insuring lifetime genetic stability. After labelling mice with (15)N-thymidine from gestation until post-natal week 8, we find no (15)N label retention by dividing small intestinal crypt cells after a four-week chase. In adult mice administered (15)N-thymidine pulse-chase, we find that proliferating crypt cells dilute the (15)N label, consistent with random strand segregation. We demonstrate the broad utility of MIMS with proof-of-principle studies of lipid turnover in Drosophila and translation to the human haematopoietic system. These studies show that MIMS provides high-resolution quantification of stable isotope labels that cannot be obtained using other techniques and that is broadly applicable to biological and medical research.
    Nature 01/2012; 481(7382):516-9. · 42.35 Impact Factor


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