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Lung Fibroblasts from Idiopathic Pulmonary Fibrosis Patients Harbor Short and Unstable Telomeres Leading to Chromosomal Instability

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  • Radhia M’kacher, GENOPOLE
  • ,
  • Madeleine Jaillet, Université de Paris
  • ,
  • Bruno Colicchio, Universite de Haute Alsace
  • ,
  • Eirini Vasarmidi, Université de Paris
  • ,
  • Arnaud Mailleux, Université de Paris
  • ,
  • Alain Dieterlen, Universite de Haute Alsace
  • ,
  • Caroline Kannengiesser, Université de Paris, Hôpital Bichat-Claude Bernard
  • ,
  • Claire Borie, Universite Paris-Saclay
  • ,
  • Noufissa Oudrhiri, Universite Paris-Saclay
  • ,
  • Steffen Junker
  • Philippe Voisin, GENOPOLE
  • ,
  • Eric Jeandidier, Groupe Hospitalier de la Région de Mulhouse Sud-Alsace
  • ,
  • Patrice Carde, Institut Gustave Roussy
  • ,
  • Michael Fenech, University of South Australia
  • ,
  • Annelise Bennaceur-Griscelli, Universite Paris-Saclay
  • ,
  • Bruno Crestani, Université de Paris, Hôpital Bichat-Claude Bernard
  • ,
  • Raphael Borie, Université de Paris, Hôpital Bichat-Claude Bernard

Idiopathic pulmonary fibrosis (IPF) is associated with several hallmarks of aging including telomere shortening, which can result from germline mutations in telomere related genes (TRGs). Here, we assessed the length and stability of telomeres as well as the integrity of chromosomes in primary lung fibroblasts from 13 IPF patients (including seven patients with pathogenic variants in TRGs) and seven controls. Automatized high-throughput detection of telomeric FISH signals highlighted lower signal intensity in lung fibroblasts from IPF patients, suggesting a telomere length defect in these cells. The increased detection of telomere loss and terminal deletion in IPF cells, particularly in TRG-mutated cells (IPF-TRG), supports the notion that these cells have unstable telomeres. Furthermore, fibroblasts from IPF patients with TRGs mutations exhibited dicentric chromosomes and anaphase bridges. Collectively, our study indicates that fibroblasts from IPF patients exhibit telomere and chromosome instability that likely contribute to the physiopathology.

Original languageEnglish
Article number310
Number of pages13
Publication statusPublished - Feb 2022

Bibliographical note

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

    Research areas

  • Anaphase bridges, Dicentric chromosome, Idiopathic pulmonary fibrosis, Micronuclei, RTEL1, Telomere dysfunction, TERT

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