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

Radhia M’kacher; Madeleine Jaillet; Bruno Colicchio; Eirini Vasarmidi; Arnaud Mailleux; Alain Dieterlen; Caroline Kannengiesser; Claire Borie; Noufissa Oudrhiri; Steffen Junker; Philippe Voisin; Eric Jeandidier; Patrice Carde; Michael Fenech; Annelise Bennaceur-Griscelli; Bruno Crestani; Raphael Borie

doi:10.3390/biomedicines10020310

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

Radhia M’kacher, Madeleine Jaillet, Bruno Colicchio, Eirini Vasarmidi, Arnaud Mailleux, Alain Dieterlen, Caroline Kannengiesser, Claire Borie, Noufissa Oudrhiri, Steffen Junker, Philippe Voisin, Eric Jeandidier, Patrice Carde, Michael Fenech, Annelise Bennaceur-Griscelli, Bruno Crestani, Raphael Borie

Department of Biomedicine - Forskning og uddannelse, Vest

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

6 Citations (Scopus)

Abstract

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 language	English
Article number	310
Journal	Biomedicines
Volume	10
Issue	2
Number of pages	13
ISSN	2227-9059
DOIs	https://doi.org/10.3390/biomedicines10020310
Publication status	Published - Feb 2022

Keywords

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

Access to Document

10.3390/biomedicines10020310Licence: CC BY

Cite this

M’kacher, R., Jaillet, M., Colicchio, B., Vasarmidi, E., Mailleux, A., Dieterlen, A., Kannengiesser, C., Borie, C., Oudrhiri, N., Junker, S., Voisin, P., Jeandidier, E., Carde, P., Fenech, M., Bennaceur-Griscelli, A., Crestani, B., & Borie, R. (2022). Lung Fibroblasts from Idiopathic Pulmonary Fibrosis Patients Harbor Short and Unstable Telomeres Leading to Chromosomal Instability. Biomedicines, 10(2), Article 310. https://doi.org/10.3390/biomedicines10020310

@article{8c75fb994ad2453ba03321dc700518b2,

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

abstract = "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.",

keywords = "Anaphase bridges, Dicentric chromosome, Idiopathic pulmonary fibrosis, Micronuclei, RTEL1, Telomere dysfunction, TERT",

author = "Radhia M{\textquoteright}kacher and Madeleine Jaillet and Bruno Colicchio and Eirini Vasarmidi and Arnaud Mailleux and Alain Dieterlen and Caroline Kannengiesser and Claire Borie and Noufissa Oudrhiri and Steffen Junker and Philippe Voisin and Eric Jeandidier and Patrice Carde and Michael Fenech and Annelise Bennaceur-Griscelli and Bruno Crestani and Raphael Borie",

note = "Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2022",

month = feb,

doi = "10.3390/biomedicines10020310",

language = "English",

volume = "10",

journal = "Biomedicines",

issn = "2227-9059",

publisher = "MDPI",

number = "2",

}

M’kacher, R, Jaillet, M, Colicchio, B, Vasarmidi, E, Mailleux, A, Dieterlen, A, Kannengiesser, C, Borie, C, Oudrhiri, N, Junker, S, Voisin, P, Jeandidier, E, Carde, P, Fenech, M, Bennaceur-Griscelli, A, Crestani, B & Borie, R 2022, 'Lung Fibroblasts from Idiopathic Pulmonary Fibrosis Patients Harbor Short and Unstable Telomeres Leading to Chromosomal Instability', Biomedicines, vol. 10, no. 2, 310. https://doi.org/10.3390/biomedicines10020310

Lung Fibroblasts from Idiopathic Pulmonary Fibrosis Patients Harbor Short and Unstable Telomeres Leading to Chromosomal Instability. / M’kacher, Radhia; Jaillet, Madeleine; Colicchio, Bruno et al.
In: Biomedicines, Vol. 10, No. 2, 310, 02.2022.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Lung Fibroblasts from Idiopathic Pulmonary Fibrosis Patients Harbor Short and Unstable Telomeres Leading to Chromosomal Instability

AU - M’kacher, Radhia

AU - Jaillet, Madeleine

AU - Colicchio, Bruno

AU - Vasarmidi, Eirini

AU - Mailleux, Arnaud

AU - Dieterlen, Alain

AU - Kannengiesser, Caroline

AU - Borie, Claire

AU - Oudrhiri, Noufissa

AU - Junker, Steffen

AU - Voisin, Philippe

AU - Jeandidier, Eric

AU - Carde, Patrice

AU - Fenech, Michael

AU - Bennaceur-Griscelli, Annelise

AU - Crestani, Bruno

AU - Borie, Raphael

PY - 2022/2

Y1 - 2022/2

N2 - 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.

AB - 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.

KW - Anaphase bridges

KW - Dicentric chromosome

KW - Idiopathic pulmonary fibrosis

KW - Micronuclei

KW - RTEL1

KW - Telomere dysfunction

KW - TERT

UR - http://www.scopus.com/inward/record.url?scp=85124103543&partnerID=8YFLogxK

U2 - 10.3390/biomedicines10020310

DO - 10.3390/biomedicines10020310

M3 - Journal article

C2 - 35203522

AN - SCOPUS:85124103543

SN - 2227-9059

VL - 10

JO - Biomedicines

JF - Biomedicines

IS - 2

M1 - 310

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this