Telomere‐associated proteins: cross‐talk between telomere maintenance and telomere‐lengthening mechanisms

Boeck, Gitte De; Forsyth, Ramses; Praet, Marleen; Hogendoorn, Pancras C.W.

doi:10.1002/path.2500

Cited by 83 publications

(68 citation statements)

References 201 publications

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“…In contrast, addition of Zscan4 resulted in 8.36-fold, 6.20-fold and 4.37-fold increases in T-SCE frequency in OSKMZ-infected MEFs on days 3, 6 and 9 post-infection ( Figure 4C and 4D), respectively. We also analyzed expression levels of shelterin components and found that Trf2, Pot1b and Rap1, which can inhibit T-SCE after replication [39,40], were repressed when Zscan4 was overexpressed ( Figure 5A). Other shelterin proteins, Trf1, Pot1a, Tpp1 and Tin2, were not repressed ( Figure 5B).…”

Section: Zscan4 Promotes Telomere Elongation During Reprogrammingmentioning

confidence: 99%

Zscan4 promotes genomic stability during reprogramming and dramatically improves the quality of iPS cells as demonstrated by tetraploid complementation

et al. 2012

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Induced pluripotent stem (iPS) cells generated using Yamanaka factors have great potential for use in autologous cell therapy. However, genomic abnormalities exist in human iPS cells, and most mouse iPS cells are not fully pluripotent, as evaluated by the tetraploid complementation assay (TCA); this is most likely associated with the DNA damage response (DDR) occurred in early reprogramming induced by Yamanaka factors. In contrast, nuclear transfer can faithfully reprogram somatic cells into embryonic stem (ES) cells that satisfy the TCA. We thus hypothesized that factors involved in oocyte-induced reprogramming may stabilize the somatic genome during reprogramming, and improve the quality of the resultant iPS cells. To test this hypothesis, we screened for factors that could decrease DDR signals during iPS cell induction. We determined that Zscan4, in combination with the Yamanaka factors, not only remarkably reduced the DDR but also markedly promoted the efficiency of iPS cell generation. The inclusion of Zscan4 stabilized the genomic DNA, resulting in p53 downregulation. Furthermore, Zscan4 also enhanced telomere lengthening as early as 3 days post-infection through a telomere recombination-based mechanism. As a result, iPS cells generated with addition of Zscan4 exhibited longer telomeres than classical iPS cells. Strikingly, more than 50% of iPS cell lines (11/19) produced via this "Zscan4 protocol" gave rise to live-borne all-iPS cell mice as determined by TCA, compared to 1/12 for lines produced using the classical Yamanaka factors. Our findings provide the first demonstration that maintaining genomic stability during reprogramming promotes the generation of high quality iPS cells.

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Section: Zscan4 Promotes Telomere Elongation During Reprogrammingmentioning

confidence: 99%

Zscan4 promotes genomic stability during reprogramming and dramatically improves the quality of iPS cells as demonstrated by tetraploid complementation

et al. 2012

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“…Without telomere protection, chromosome ends activate DNA damage response pathways that signal cell-cycle arrest, senescence or apoptosis. [4][5][6] Short telomeres in peripheral blood have been described in obese and diabetic patients and in individuals with cardiovascular risk factors, that is, increased blood pressure, increased carotid intima media thickness, smoking as well as in response to psychosocial stress. [7][8][9][10] Telomere length, in vivo as well as in vitro, can be considered as a biological marker for age-and stress-related conditions.…”

Section: Introductionmentioning

confidence: 99%

Telomere length of subcutaneous adipose tissue cells is shorter in obese and formerly obese subjects

et al. 2010

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Obesity and increased fat mass are associated with increased adipocyte proliferation. Telomere length can serve as a biomarker of a cell's biological (vs chronological) age. To gain insight in the physiology of adipose tissue, we aimed to investigate telomere length in subcutaneous adipose tissue in relation to age and obesity. Telomere length was measured in 72 subcutaneous adipose tissue samples from 21 nonobese and 51 obese subjects. Telomere length of subcutaneous adipose tissue cells was negatively associated with body mass index (BMI), systolic blood pressure and fasting triglycerides. After controlling for age, fasting glucose, triglycerides and smoking status, BMI (P ¼ 0.009) contributed independently to 16% of telomere length variance. Interestingly, formerly obese patients (n ¼ 10) had shorter telomere length than never-obese subjects (n ¼ 12) of similar age, sex and BMI (7.1 ± 1.3 vs 9.08 ± 1.8 kb, P ¼ 0.01). In summary, adipose tissue cells from obese subjects show a shorter telomere length. The shorter telomere length of formerly obese subjects suggests that this is an established, irreversible feature of obesity that could contribute to its comorbidities.

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“…Telomerase is a ribonucleoprotein complex consisting of a catalytic protein component (hTERT) and a RNA component (TERC), that compensate for telomere attrition by adding repeats onto chromosome ends (8). Its activity is normally not detectable in most adult tissues, apart from stem cells of proliferative tissues.…”

Section: Introductionmentioning

confidence: 99%

The role of TERT-CLPTM1L SNPs, hTERT expression and telomere length in the pathogenesis of oral squamous cell carcinoma

et al. 2016

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The aim of this study was to assess TERT-CLPTM1L single-nucleotide polymorphisms (SNPs) (rs402710 C/T in the CLPTM1L gene; rs2736100 A/C and rs2736098 G/A in the TERT gene) as risk factors for development of oral squamous cell carcinoma (OSCC), and to investigate the relationship between the analyzed polymorphisms, relative telomere length (RTL), telomerase expression and clinicopathologic characteristics of OSCC in a Serbian population. Paraffin-embedded tumor samples and buccal swabs from cancer-free controls were genotyped using PCR-RFLP, while tumor RTL values and telomerase expression were estimated by real-time PCR and immunohistochemistry, respectively. CLPTM1L rs402710 and TERT rs2736100 polymorphisms were associated with a significantly increased risk of OSCC, and TERT rs2736098 with a significantly decreased risk. No significant association was found between TERT-CLPTM1L polymorphisms, tumor RTL values, telomerase expression, and clinicopathologic features, although a trend towards longer telomeres was evident in telomerase-positive samples and less advanced tumors. Kaplan-Meier survival analysis showed that patients with longer telomeres in their tumors had significantly better overall survival than patients with shorter telomeres. Our research seems to provide strong evidence for an association between CLPTM1L rs402710C/T and TERT rs2736100A/C SNPs and the risk of OSSC, and suggests that higher tumor RTL values and positive hTERT expression may be applicable as early prognostic markers. (J Oral Sci 58, [449][450][451][452][453][454][455][456][457][458] 2016)

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Telomere‐associated proteins: cross‐talk between telomere maintenance and telomere‐lengthening mechanisms

Cited by 83 publications

References 201 publications

Zscan4 promotes genomic stability during reprogramming and dramatically improves the quality of iPS cells as demonstrated by tetraploid complementation

Zscan4 promotes genomic stability during reprogramming and dramatically improves the quality of iPS cells as demonstrated by tetraploid complementation

Telomere length of subcutaneous adipose tissue cells is shorter in obese and formerly obese subjects

The role of TERT-CLPTM1L SNPs, hTERT expression and telomere length in the pathogenesis of oral squamous cell carcinoma

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