dc.contributor.author | Lipskaia, Larissa | |
dc.contributor.author | Breau, Marielle | |
dc.contributor.author | Cayrou, Christelle | |
dc.contributor.author | Churikov, Dmitri | |
dc.contributor.author | Braud, Laura | |
dc.contributor.author | Jacquet, Juliette | |
dc.contributor.author | Born, Emmanuelle | |
dc.contributor.author | Fouillade, Charles | |
dc.contributor.author | Curras-Alonso, Sandra | |
dc.contributor.author | Bauwens, Serge | |
dc.contributor.author | Jourquin, Frederic | |
dc.contributor.author | Fiore, Frederic | |
dc.contributor.author | Castellano, Rémy | |
dc.contributor.author | Josselin, Emmanuelle | |
dc.contributor.author | Sánchez-Ferrer, Carlota | |
dc.contributor.author | Giovinazzo, Giovanna | |
dc.contributor.author | Lachaud, Christophe | |
dc.contributor.author | Gilson, Eric | |
dc.contributor.author | Flores, Ignacio | |
dc.contributor.author | Londono-Vallejo, Arturo | |
dc.contributor.author | Adnot, Serge | |
dc.contributor.author | Géli, Vincent | |
dc.date.accessioned | 2024-07-04T09:12:08Z | |
dc.date.available | 2024-07-04T09:12:08Z | |
dc.date.issued | 2024-03 | |
dc.identifier.citation | EMBO Rep. 2024 Mar;25(3):1650-1684. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/20039 | |
dc.description.abstract | Lung diseases develop when telomeres shorten beyond a critical point. We constructed a mouse model in which the catalytic subunit of telomerase (mTert), or its catalytically inactive form (mTertCI), is expressed from the p21Cdkn1a locus. Expression of either TERT or TERTCI reduces global p21 levels in the lungs of aged mice, highlighting TERT non-canonical function. However, only TERT reduces accumulation of very short telomeres, oxidative damage, endothelial cell (ECs) senescence and senile emphysema in aged mice. Single-cell analysis of the lung reveals that p21 (and hence TERT) is expressed mainly in the capillary ECs. We report that a fraction of capillary ECs marked by CD34 and endowed with proliferative capacity declines drastically with age, and this is counteracted by TERT but not TERTCI. Consistently, only TERT counteracts decline of capillary density. Natural aging effects are confirmed using the experimental model of emphysema induced by VEGFR2 inhibition and chronic hypoxia. We conclude that catalytically active TERT prevents exhaustion of the putative CD34 + EC progenitors with age, thus protecting against capillary vessel loss and pulmonary emphysema. | es_ES |
dc.description.sponsorship | We thank Lea Harrington for providing mTert-/- mouse ES cells. We are very
grateful to Myriam Grunewald (Hebrew University of Jerusalem) for critically
reading the manuscript. We are grateful to the CRCM animal facility for taking
care of the mouse strain colonies, to Manon Richaud from the CRCM flow
cytometry and cell-sorting platform, and to Lionel Spinelli and Arnaud Guille
for useful discussions and technical support for the single-cell analysis. We
thank the Institut Curie Bioinformatics platform for data management and
quality control of single-cell data and the CRCM DNA Damage Platform and
Imaging facility. Work in VG’s Lab is supported by “La Ligue Contre le Cancer”,
Equipe Labellisée, The Canceropole PACA (Projet Emergent), the “Institut
National du Cancer” (INCA), PLBIO 2019, and the cross-cutting Inserm
program on aging (AGEMED). SA’s Lab is supported by grants from the Inserm,
Ministère de la Recherche, Agence Nationale pour la Recherche (ANR), Institut
National du Cancer (INCA), and Fondation pour la Recherche Médicale (FRM),
et la Fondation ARC. AL-V’s lab is supported by INCa (PLBIO2019) and La
Ligue contre le cancer-Paris (RS21/75-24). SC-A is a recipient of a European
CO-FUND PhD fellowship from Institut Curie (European Union’s Horizon 2020
research and innovation program under the Marie Skłodowska-Curie grant
agreement No 666003). IF’s lab was funded by grants from the Spanish
Ministry of Science and Innovation (PID2019-110339RB-I00) and the
Comunidad de Madrid (S2017/BMD-3875). EG’s lab was supported by the
Fondation ARC (Program ARC), and the cross-cutting Inserm program on aging
(AGEMED). CIPHE is supported by PHENOMIN (French National Infrastructure
for mouse Phenogenomics; ANR10-INBS-07). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Wiley | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject.mesh | Pulmonary Emphysema | es_ES |
dc.subject.mesh | Microvascular Rarefaction | es_ES |
dc.subject.mesh | Emphysema | es_ES |
dc.subject.mesh | Telomerase | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Telomere Shortening | es_ES |
dc.title | mTert induction in p21-positive cells counteracts capillary rarefaction and pulmonary emphysema. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 38424230 | es_ES |
dc.format.volume | 25 | es_ES |
dc.format.number | 3 | es_ES |
dc.format.page | 1650 | es_ES |
dc.identifier.doi | 10.1038/s44319-023-00041-1 | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | es_ES |
dc.contributor.funder | Comunidad de Madrid (España) | es_ES |
dc.contributor.funder | Unión Europea. Comisión Europea. H2020 | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1469-3178 | es_ES |
dc.relation.publisherversion | 10.1038/s44319-023-00041-1 | es_ES |
dc.identifier.journal | EMBO reports | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Tecnología de Células Pluripotentes | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PID2019-110339RB-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/S2017/BMD-3875 | es_ES |