High-resolution telomere fluorescence in situ hybridization reveals intriguing anomalies in germ cell tumors

Shekhani, Mohammed Talha; Barber, John R.; Bezerra, Stephania M.; Heaphy, Christopher M.; Roibon, Nilda Diana Gonzalez; Taheri, Diana; Reis, Leonardo Oliveira; Güner, Güneş; Joshu, Corinne E.; Netto, George J.; Meeker, Alan K.

doi:10.1016/j.humpath.2016.03.015

Cited by 7 publications

(5 citation statements)

References 32 publications

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“…It revealed that the majority of NSE tumors showed TL elongation, whereas TL shortening was dominant in SE tumors. This is consistent with a recent study using fluorescence in situ hybridization [30]. Therefore, the result of TL distribution, which were lengthening in NSE and shortening in SE, is consistent regardless of measurement technique.…”

Section: Systematic Tl Difference Between Nse and Sesupporting

confidence: 92%

Distinct telomere length and molecular signatures in seminoma and non-seminoma of testicular germ cell tumor

Sun

Kim

Jia

et al. 2018

Briefings in Bioinformatics

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Testicular germ cell tumors (TGCTs) are classified into two main subtypes, seminoma (SE) and non-seminoma (NSE), but their molecular distinctions remain largely unexplored. Here, we used expression data for mRNAs and microRNAs (miRNAs) from The Cancer Genome Atlas (TCGA) to perform a systematic investigation to explain the different telomere length (TL) features between NSE (n = 48) and SE (n = 55). We found that TL elongation was dominant in NSE, whereas TL shortening prevailed in SE. We further showed that both mRNA and miRNA expression profiles could clearly distinguish these two subtypes. Notably, four telomere-related genes (TelGenes) showed significantly higher expression and positively correlated with telomere elongation in NSE than SE: three telomerase activity-related genes (TERT, WRAP53 and MYC) and an independent telomerase activity gene (ZSCAN4). We also found that the expression of genes encoding Yamanaka factors was positively correlated with telomere lengthening in NSE. Among them, SOX2 and MYC were highly expressed in NSE versus SE, while POU5F1 and KLF4 had the opposite patterns. These results suggested that enhanced expression of both TelGenes (TERT, WRAP53, MYC and ZSCAN4) and Yamanaka factors might induce telomere elongation in NSE. Conversely, the relative lack of telomerase activation and low expression of independent telomerase activity pathway during cell division may be contributed to telomere shortening in SE. Taken together, our results revealed the potential molecular profiles and regulatory roles involving the TL difference between NSE and SE, and provided a better molecular understanding of this complex disease.

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Section: Systematic Tl Difference Between Nse and Sesupporting

confidence: 92%

Distinct telomere length and molecular signatures in seminoma and non-seminoma of testicular germ cell tumor

Sun

Kim

Jia

et al. 2018

Briefings in Bioinformatics

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“…The investigators were blinded during experimental procedures, imaging acquisition, and analysis. TL was measured using the Software for Telomere Counting (developed at Johns Hopkins, http://demarzolab.pathology.jhmi.edu/telometer/) as previously described . Briefly, the nuclear area (using the DAPI staining) of the cell type of interest is identified.…”

Section: Methodsmentioning

confidence: 99%

“…Invaluable to our understanding of telomere dynamics are tissue‐ and cell‐specific analyses of telomeres in human diseased and nondiseased hearts using high‐resolution methods. Telomere quantitative fluorescence in situ hybridization (Q‐FISH) allows TL assessments in paraffin‐embedded archival material, while providing single‐cell resolution and maintaining intact tissue architecture . Although successfully used on a number of tissues, telomere Q‐FISH was only recently optimized for cardiac tissues .…”

Section: Introductionmentioning

confidence: 99%

Cardiomyocyte‐Specific Telomere Shortening is a Distinct Signature of Heart Failure in Humans

Sharifi‐Sanjani

Oyster

Tichy

et al. 2017

JAHA

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BackgroundTelomere defects are thought to play a role in cardiomyopathies, but the specific cell type affected by the disease in human hearts is not yet identified. The aim of this study was to systematically evaluate the cell type specificity of telomere shortening in patients with heart failure in relation to their cardiac disease, age, and sex.Methods and ResultsWe studied cardiac tissues from patients with heart failure by utilizing telomere quantitative fluorescence in situ hybridization, a highly sensitive method with single‐cell resolution. In this study, total of 63 human left ventricular samples, including 37 diseased and 26 nonfailing donor hearts, were stained for telomeres in combination with cardiomyocyte‐ or α‐smooth muscle cell‐specific markers, cardiac troponin T, and smooth muscle actin, respectively, and assessed for telomere length. Patients with heart failure demonstrate shorter cardiomyocyte telomeres compared with nonfailing donors, which is specific only to cardiomyocytes within diseased human hearts and is associated with cardiomyocyte DNA damage. Our data further reveal that hypertrophic hearts with reduced ejection fraction exhibit the shortest telomeres. In contrast to other reported cell types, no difference in cardiomyocyte telomere length is evident with age. However, under the disease state, telomere attrition manifests in both young and older patients with cardiac hypertrophy. Finally, we demonstrate that cardiomyocyte‐telomere length is better sustained in women than men under diseased conditions.ConclusionsThis study provides the first evidence of cardiomyocyte‐specific telomere shortening in heart failure.

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“…The effect of telomere length on maintaining tissue homeostasis and stem cell function has been studied in many tissues ( Flores and Blasco, 2010 , Flores et al., 2008 , Morrison et al., 1996 , Sekulovic et al., 2011 , Shekhani et al., 2016 ). However, in the skeletal muscle field, existing methods are not well suited for stem cell analysis due to technical and biological limitations of the muscles (rare population, fragile cells, no MuSC expansion, and small tissue sample availability).…”

Section: Resultsmentioning

confidence: 99%

Single Stem Cell Imaging and Analysis Reveals Telomere Length Differences in Diseased Human and Mouse Skeletal Muscles

et al. 2017

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SummaryMuscle stem cells (MuSCs) contribute to muscle regeneration following injury. In many muscle disorders, the repeated cycles of damage and repair lead to stem cell dysfunction. While telomere attrition may contribute to aberrant stem cell functions, methods to accurately measure telomere length in stem cells from skeletal muscles have not been demonstrated. Here, we have optimized and validated such a method, named MuQ-FISH, for analyzing telomere length in MuSCs from either mice or humans. Our analysis showed no differences in telomere length between young and aged MuSCs from uninjured wild-type mice, but MuSCs isolated from young dystrophic mice exhibited significantly shortened telomeres. In corroboration, we demonstrated that telomere attrition is present in human dystrophic MuSCs, which underscores its importance in diseased regenerative failure. The robust technique described herein provides analysis at a single-cell resolution and may be utilized for other cell types, especially rare populations of cells.

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High-resolution telomere fluorescence in situ hybridization reveals intriguing anomalies in germ cell tumors

Cited by 7 publications

References 32 publications

Distinct telomere length and molecular signatures in seminoma and non-seminoma of testicular germ cell tumor

Distinct telomere length and molecular signatures in seminoma and non-seminoma of testicular germ cell tumor

Cardiomyocyte‐Specific Telomere Shortening is a Distinct Signature of Heart Failure in Humans

Single Stem Cell Imaging and Analysis Reveals Telomere Length Differences in Diseased Human and Mouse Skeletal Muscles

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