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Common Telomere Changes during In Vivo Reprogramming and Early Stages of Tumorigenesis.

ABSTRACT: Reprogramming of differentiated cells into induced pluripotent stem cells has been recently achieved in vivo in mice. Telomeres are essential for chromosomal stability and determine organismal life span as well as cancer growth. Here, we study whether tissue dedifferentiation induced by in vivo reprogramming involves changes at telomeres. We find telomerase-dependent telomere elongation in the reprogrammed areas. Notably, we found highly upregulated expression of the TRF1 telomere protein in the reprogrammed areas, which was independent of telomere length. Moreover, TRF1 inhibition reduced in vivo reprogramming efficiency. Importantly, we extend the finding of TRF1 upregulation to pathological tissue dedifferentiation associated with neoplasias, in particular during pancreatic acinar-to-ductal metaplasia, a process that involves transdifferentiation of adult acinar cells into ductal-like cells due to K-Ras oncogene expression. These findings place telomeres as important players in cellular plasticity both during in vivo reprogramming and in pathological conditions associated with increased plasticity, such as cancer.

SUBMITTER: Marion RM

PROVIDER: S-EPMC5312258 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Common Telomere Changes during In Vivo Reprogramming and Early Stages of Tumorigenesis.

Marión Rosa M RM López de Silanes Isabel I Mosteiro Lluc L Gamache Benjamin B Abad María M Guerra Carmen C Megías Diego D Serrano Manuel M Blasco Maria A MA

Stem cell reports 20170202 2

Reprogramming of differentiated cells into induced pluripotent stem cells has been recently achieved in vivo in mice. Telomeres are essential for chromosomal stability and determine organismal life span as well as cancer growth. Here, we study whether tissue dedifferentiation induced by in vivo reprogramming involves changes at telomeres. We find telomerase-dependent telomere elongation in the reprogrammed areas. Notably, we found highly upregulated expression of the TRF1 telomere protein in the ...[more]

PMID: 28162998

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Project description:Pea (Pisum sativum L.) is an important source of dietary proteins. Nutrient recycling from leaves contributes to the accumulation of seed proteins and is a pivotal determinant of protein yields in this grain legume. The aim of this study was to unveil the transcriptional regulations occurring in pea leaves before the sharp decrease in chlorophyll breakdown. As a prelude to this study, a time-series analysis of 15N translocation at the whole plant level was performed, which indicated that nitrogen recycling among organs was highly dynamic during this period and varied depending on nitrate availability. Leaves collected on vegetative and reproductive nodes were further analyzed by transcriptomics. The data revealed extensive transcriptome changes in leaves of reproductive nodes during early seed development (from flowering to 14 days after flowering), including an up-regulation of genes encoding transporters, and particularly of sulfate that might sustain sulfur metabolism in leaves of the reproductive part. This developmental period was also characterized by a down-regulation of cell wall-associated genes in leaves of both reproductive and vegetative nodes, reflecting a shift in cell wall structure. Later on, 27 days after flowering, genes potentially switching the metabolism of leaves toward senescence were pinpointed, some of which are related to ribosomal RNA processing, autophagy, or transport systems. Transcription factors differentially regulated in leaves between stages were identified and a gene co-expression network pointed out some of them as potential regulators of the above-mentioned biological processes. The same approach was conducted in Medicago truncatula to identify shared regulations with this wild legume species. Altogether the results give a global view of transcriptional events in leaves of legumes at early reproductive stages and provide a valuable resource of candidate genes that could be targeted by reverse genetics to improve nutrient remobilization and/or delay catabolic processes leading to senescence.

Dataset Information

Common Telomere Changes during In Vivo Reprogramming and Early Stages of Tumorigenesis.

Publications

Common Telomere Changes during In Vivo Reprogramming and Early Stages of Tumorigenesis.

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