Telomeres in Trisomy 21 Amniocytes

Sukenik-Halevy, Rivka; Biron‐Shental, Tal; Sharony, Reuven; Fejgin, Moshe D.; Amiel, Aliza

doi:10.1159/000329714

Cited by 19 publications

(11 citation statements)

References 131 publications

(66 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, iPSCs and neurons derived from monozygotic discordant twins shed light on several phenotypic abnormalities in DS stem cells, including cell proliferation delay, excitatory/inhibitory transmission imbalance and higher sensitivity to oxidative stress induced apoptosis, some of which were impossible to assess directly in the brain of humans with DS75051. Similar to the iPSCs, amniocytes from fetuses with DS display cell proliferation defects, early senescence and shorter telomeres compared to euploid fetuses525354.…”

Section: Discussionmentioning

confidence: 99%

An Integrated Human/Murine Transcriptome and Pathway Approach To Identify Prenatal Treatments For Down Syndrome

Guedj

Pennings

Massingham

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Anatomical and functional brain abnormalities begin during fetal life in Down syndrome (DS). We hypothesize that novel prenatal treatments can be identified by targeting signaling pathways that are consistently perturbed in cell types/tissues obtained from human fetuses with DS and mouse embryos. We analyzed transcriptome data from fetuses with trisomy 21, age and sex-matched euploid controls, and embryonic day 15.5 forebrains from Ts1Cje, Ts65Dn, and Dp16 mice. The new datasets were compared to other publicly available datasets from humans with DS. We used the human Connectivity Map (CMap) database and created a murine adaptation to identify FDA-approved drugs that can rescue affected pathways. USP16 and TTC3 were dysregulated in all affected human cells and two mouse models. DS-associated pathway abnormalities were either the result of gene dosage specific effects or the consequence of a global cell stress response with activation of compensatory mechanisms. CMap analyses identified 56 molecules with high predictive scores to rescue abnormal gene expression in both species. Our novel integrated human/murine systems biology approach identified commonly dysregulated genes and pathways. This can help to prioritize therapeutic molecules on which to further test safety and efficacy. Additional studies in human cells are ongoing prior to pre-clinical prenatal treatment in mice.

show abstract

Section: Discussionmentioning

confidence: 99%

An Integrated Human/Murine Transcriptome and Pathway Approach To Identify Prenatal Treatments For Down Syndrome

Guedj

Pennings

Massingham

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…These were subjects who did not have a fetus with IUGR and who had undergone prenatal diagnosis for advanced maternal age, second trimester maternal serum screening (risk >1/250 of having a child with trisomy 21), family history of chromosome or gene abnormalities (prenatal diagnosis for “antecedent”), isolated anomaly under ultrasound, and who were non-smokers (controls). As telomere length was shown to be reduced in trisomy 21 amniocytes, cases and controls were informed of the possibility of finding a cytogenetic abnormality with the Fluorescence In Situ Hybridization (FISH) technique to detect the main aneuploidies and/or after the conventional karyotyping and that they would be excluded from this study if so [20].…”

Section: Methodsmentioning

confidence: 99%

Reduced Placental Telomere Length during Pregnancies Complicated by Intrauterine Growth Restriction

et al. 2013

View full text Add to dashboard Cite

ObjectivesRecent studies have shown that telomere length was significantly reduced in placentas collected at delivery from pregnancies complicated by intrauterine growth restriction secondary to placental insufficiency. Placental telomere length measurement during ongoing pregnancies complicated by intrauterine growth restriction has never been reported. This was the main objective of our study.MethodsIn our center, late chorionic villus samplings were performed between 18 and 37 weeks of amenorrhea in 24 subjects with severe intrauterine growth restriction (cases) and in 28 subjects with other indications for prenatal diagnosis (controls). Placental insufficiency was assessed by histo-pathological examination. Relative measurement of telomere length was carried out prospectively by quantitative Fluorescent In Situ Hybridization using fluorescent Peptide Nucleic Acid probes on interphase nuclei obtained from long-term cultured villi and with an automated epifluorescent microscope. A quantitative Polymerase Chain Reaction technique was performed to confirm the quantitative Fluorescent In Situ Hybridization results. The number of copies of gene loci encoding the RNA template (hTERC) and the catalytic subunit (hTERT) of the enzyme complex telomerase were also estimated in these placentas by Fluorescent In Situ Hybridization.ResultsMean fluorescence intensity of telomere probes estimated by quantitative Fluorescent In Situ Hybridization was significantly less for cases compared to controls (p<0.001). This result indicated that mean telomere length was significantly reduced in placentas during pregnancies complicated by intrauterine growth restriction. Reduced telomere length was confirmed by the quantitative Polymerase Chain Reaction technique. No copy number variation of the hTERC and hTERT loci was noticed for cases, or for controls.ConclusionThis study clearly demonstrates a reduction of placental telomere length in ongoing pregnancies (from 18 to 37 weeks of amenorrhea) complicated by severe intrauterine growth restriction secondary to placental insufficiency.

show abstract

“…Among these characteristics is random aneuploidy of chromosomes in addition to the one defining the aneuploidy, shorter telomeres (Vaziri et al, 1993), and increased telomere aggregates (Hadi et al, 2009). In a previous study (Sukenik-Halevy et al, 2011), we found increased TERC copy number in amniocytes from five individuals with trisomy 21. The increased rate was found on chromosome 3 and other chromosomes.…”

Section: Introductionmentioning

confidence: 50%

“…Telomerase activity was reported in megakaryoblastic leukemia, the most common leukemia in Down syndrome (Holt et al, 1991). Our previous observation of an amplification of TERC, the gene encoding one of the components of telomerase, might imply a connection between a genomic instability process that takes place in trisomy 21 and an over-expression of telomerase (Sukenik-Halevy et al, 2011).…”

Section: Discussionmentioning

confidence: 83%

Increased TERC gene copy number in amniocytes from fetuses with trisomy 18 or a sex chromosome aneuploidy

Biron‐Shental

Kitay-Cohen

Tene

et al. 2012

Gene

View full text Add to dashboard Cite

Telomeres in Trisomy 21 Amniocytes

Cited by 19 publications

References 131 publications

An Integrated Human/Murine Transcriptome and Pathway Approach To Identify Prenatal Treatments For Down Syndrome

An Integrated Human/Murine Transcriptome and Pathway Approach To Identify Prenatal Treatments For Down Syndrome

Reduced Placental Telomere Length during Pregnancies Complicated by Intrauterine Growth Restriction

Increased TERC gene copy number in amniocytes from fetuses with trisomy 18 or a sex chromosome aneuploidy

Contact Info

Product

Resources

About