Hematopoiesis under telomere attrition at the single-cell resolution

Thongon, N. (Natthakan)|||/items/514e85a7-885f-4b16-a604-764b22dcefa5; Ma, F. (Feiyang)|||/items/7ede2a67-0437-4766-9856-d9155d1c854c; Santoni, A. (Andrea)|||/items/d547cac2-df37-441e-b1ac-37766435e274; Marchesini, M. (Matteo)|||/items/a316eef8-b4b4-4e35-8cd8-37e19fa17d35; Fiorini, E. (Elena)|||/items/7d56cffc-1272-4194-b43b-ea86cf9f7a72; Rose, A. (Ashley)|||/items/9d1d6da5-6f11-4d48-853f-5ca8b9bf0e51; Adema, V. (Vera)|||/items/08bca88e-5689-472d-87e8-4c5e1deafdf3; Gañán-Gómez, I. (Irene)|||/items/92d1787d-8a7f-414a-af8a-a0cc2094a8af; Groarke, E.M. (Emma M.)|||/items/31a9e9a4-160c-4855-912e-5aef460d67fe; Gutiérrez-Rodrigues, F. (Fernanda)|||/items/153ead07-eab7-4d54-89a5-342692717984; Chen, S. (Shuaitong)|||/items/1e824da5-11e2-4486-9d90-80b38cb404ef; Lockyer, P. (Pamela)|||/items/69f07a1c-2641-43a7-a665-4dedefefcd41; Schneider, S. (Sarah)|||/items/6d46d5a8-7d75-456d-8c8d-3f363830dfd8; Bueso-Ramos, C. (Carlos)|||/items/b7083c64-9627-4e7b-a6ba-3364acb2fa21; Montalbán-Bravo, G. (Guillermo)|||/items/e911736a-66b9-4e64-9d5c-4475f6a6e61b; Class, C.A. (Caleb A.)|||/items/4294f0fc-a5bd-4a32-b316-06eef51d3d1b; Soltysiak, K.A. (Kelly A.)|||/items/a9cf551e-ccfe-4c48-88dd-d7d4df9bbc1f; Pellegrini, M.M. (Massimiliano Matteo)|||/items/b2629cd3-e142-4554-94fe-f9b652fb06fe; Sahin, E. (Ergun)|||/items/a1432990-ae1a-431e-80fe-4f13ee56367e; Bertuch, A.A. (Alison A.)|||/items/029fdb38-dcf8-4e2b-b836-de42d5dbba2b; DiNardo, C.D. (Courtney D.)|||/items/b7fb579c-78d6-47b0-b007-d1b9e2170587; Garcia-Manero, G. (Guillermo)|||/items/e2797ef5-c469-437c-afb3-e178412217ce; Young, N.S. (Neal S.)|||/items/764eec3c-5bff-48ad-b4ec-1ae3492c7339; Dwyer, K. (Karen)|||/items/6a9f7805-c16f-4030-9ad1-ac71d3c360ad; Colla, S. (Simona)|||/items/659f9e93-5695-4c4a-948e-85565d696acc

Hematopoiesis under telomere attrition at the single-cell resolution

The molecular mechanisms that drive hematopoietic stem cell functional decline under conditions of telomere shortening are not completely understood. In light of recent advances in single-cell technologies, we sought to redefine the transcriptional and epigenetic landscape of mouse and human hematop...

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Detalles Bibliográficos
Autores:	Thongon, N. (Natthakan)\|\|\|/items/514e85a7-885f-4b16-a604-764b22dcefa5, Ma, F. (Feiyang)\|\|\|/items/7ede2a67-0437-4766-9856-d9155d1c854c, Santoni, A. (Andrea)\|\|\|/items/d547cac2-df37-441e-b1ac-37766435e274, Marchesini, M. (Matteo)\|\|\|/items/a316eef8-b4b4-4e35-8cd8-37e19fa17d35, Fiorini, E. (Elena)\|\|\|/items/7d56cffc-1272-4194-b43b-ea86cf9f7a72, Rose, A. (Ashley)\|\|\|/items/9d1d6da5-6f11-4d48-853f-5ca8b9bf0e51, Adema, V. (Vera)\|\|\|/items/08bca88e-5689-472d-87e8-4c5e1deafdf3, Gañán-Gómez, I. (Irene)\|\|\|/items/92d1787d-8a7f-414a-af8a-a0cc2094a8af, Groarke, E.M. (Emma M.)\|\|\|/items/31a9e9a4-160c-4855-912e-5aef460d67fe, Gutiérrez-Rodrigues, F. (Fernanda)\|\|\|/items/153ead07-eab7-4d54-89a5-342692717984, Chen, S. (Shuaitong)\|\|\|/items/1e824da5-11e2-4486-9d90-80b38cb404ef, Lockyer, P. (Pamela)\|\|\|/items/69f07a1c-2641-43a7-a665-4dedefefcd41, Schneider, S. (Sarah)\|\|\|/items/6d46d5a8-7d75-456d-8c8d-3f363830dfd8, Bueso-Ramos, C. (Carlos)\|\|\|/items/b7083c64-9627-4e7b-a6ba-3364acb2fa21, Montalbán-Bravo, G. (Guillermo)\|\|\|/items/e911736a-66b9-4e64-9d5c-4475f6a6e61b, Class, C.A. (Caleb A.)\|\|\|/items/4294f0fc-a5bd-4a32-b316-06eef51d3d1b, Soltysiak, K.A. (Kelly A.)\|\|\|/items/a9cf551e-ccfe-4c48-88dd-d7d4df9bbc1f, Pellegrini, M.M. (Massimiliano Matteo)\|\|\|/items/b2629cd3-e142-4554-94fe-f9b652fb06fe, Sahin, E. (Ergun)\|\|\|/items/a1432990-ae1a-431e-80fe-4f13ee56367e, Bertuch, A.A. (Alison A.)\|\|\|/items/029fdb38-dcf8-4e2b-b836-de42d5dbba2b, DiNardo, C.D. (Courtney D.)\|\|\|/items/b7fb579c-78d6-47b0-b007-d1b9e2170587, Garcia-Manero, G. (Guillermo)\|\|\|/items/e2797ef5-c469-437c-afb3-e178412217ce, Young, N.S. (Neal S.)\|\|\|/items/764eec3c-5bff-48ad-b4ec-1ae3492c7339, Dwyer, K. (Karen)\|\|\|/items/6a9f7805-c16f-4030-9ad1-ac71d3c360ad, Colla, S. (Simona)\|\|\|/items/659f9e93-5695-4c4a-948e-85565d696acc
Tipo de recurso:	artículo
Fecha de publicación:	2021
País:	España
Institución:	Universidad de Navarra
Repositorio:	Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:	inglés
OAI Identifier:	oai:dadun.unav.edu:10171/121384
Acceso en línea:	https://hdl.handle.net/10171/121384
Access Level:	acceso abierto
Palabra clave:	molecular mechanisms hematopoietic stem cell functional decline single-cell technologies

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network_acronym_str	ES
network_name_str	España
repository_id_str
spelling	Hematopoiesis under telomere attrition at the single-cell resolutionThongon, N. (Natthakan)\|\|\|/items/514e85a7-885f-4b16-a604-764b22dcefa5Ma, F. (Feiyang)\|\|\|/items/7ede2a67-0437-4766-9856-d9155d1c854cSantoni, A. (Andrea)\|\|\|/items/d547cac2-df37-441e-b1ac-37766435e274Marchesini, M. (Matteo)\|\|\|/items/a316eef8-b4b4-4e35-8cd8-37e19fa17d35Fiorini, E. (Elena)\|\|\|/items/7d56cffc-1272-4194-b43b-ea86cf9f7a72Rose, A. (Ashley)\|\|\|/items/9d1d6da5-6f11-4d48-853f-5ca8b9bf0e51Adema, V. (Vera)\|\|\|/items/08bca88e-5689-472d-87e8-4c5e1deafdf3Gañán-Gómez, I. (Irene)\|\|\|/items/92d1787d-8a7f-414a-af8a-a0cc2094a8afGroarke, E.M. (Emma M.)\|\|\|/items/31a9e9a4-160c-4855-912e-5aef460d67feGutiérrez-Rodrigues, F. (Fernanda)\|\|\|/items/153ead07-eab7-4d54-89a5-342692717984Chen, S. (Shuaitong)\|\|\|/items/1e824da5-11e2-4486-9d90-80b38cb404efLockyer, P. (Pamela)\|\|\|/items/69f07a1c-2641-43a7-a665-4dedefefcd41Schneider, S. (Sarah)\|\|\|/items/6d46d5a8-7d75-456d-8c8d-3f363830dfd8Bueso-Ramos, C. (Carlos)\|\|\|/items/b7083c64-9627-4e7b-a6ba-3364acb2fa21Montalbán-Bravo, G. (Guillermo)\|\|\|/items/e911736a-66b9-4e64-9d5c-4475f6a6e61bClass, C.A. (Caleb A.)\|\|\|/items/4294f0fc-a5bd-4a32-b316-06eef51d3d1bSoltysiak, K.A. (Kelly A.)\|\|\|/items/a9cf551e-ccfe-4c48-88dd-d7d4df9bbc1fPellegrini, M.M. (Massimiliano Matteo)\|\|\|/items/b2629cd3-e142-4554-94fe-f9b652fb06feSahin, E. (Ergun)\|\|\|/items/a1432990-ae1a-431e-80fe-4f13ee56367eBertuch, A.A. (Alison A.)\|\|\|/items/029fdb38-dcf8-4e2b-b836-de42d5dbba2bDiNardo, C.D. (Courtney D.)\|\|\|/items/b7fb579c-78d6-47b0-b007-d1b9e2170587Garcia-Manero, G. (Guillermo)\|\|\|/items/e2797ef5-c469-437c-afb3-e178412217ceYoung, N.S. (Neal S.)\|\|\|/items/764eec3c-5bff-48ad-b4ec-1ae3492c7339Dwyer, K. (Karen)\|\|\|/items/6a9f7805-c16f-4030-9ad1-ac71d3c360adColla, S. (Simona)\|\|\|/items/659f9e93-5695-4c4a-948e-85565d696accmolecular mechanismshematopoietic stem cell functional declinesingle-cell technologiesThe molecular mechanisms that drive hematopoietic stem cell functional decline under conditions of telomere shortening are not completely understood. In light of recent advances in single-cell technologies, we sought to redefine the transcriptional and epigenetic landscape of mouse and human hematopoietic stem cells under telomere attrition, as induced by pathogenic germline variants in telomerase complex genes. Here, we show that telomere attrition maintains hematopoietic stem cells under persistent metabolic activation and differentiation towards the megakaryocytic lineage through the cell-intrinsic upregulation of the innate immune signaling response, which directly compromises hematopoietic stem cells’ self-renewal capabilities and eventually leads to their exhaustion. Mechanistically, we demonstrate that targeting members of the Ifi20x/IFI16 family of cytosolic DNA sensors using the oligodeoxynucleotide A151, which comprises four repeats of the TTAGGG motif of the telomeric DNA, overcomes interferon signaling activation in telomere-dysfunctional hematopoietic stem cells and these cells’ skewed differentiation towards the megakaryocytic lineage. This study challenges the historical hypothesis that telomere attrition limits the proliferative potential of hematopoietic stem cells by inducing apoptosis, autophagy, or senescence, and suggests that targeting IFI16 signaling axis might prevent hematopoietic stem cell functional decline in conditions affecting telomere maintenance.NatureDadun. Depósito Académico Digital Universidad de Navarra20212021-01-0120212021-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/121384reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/1213842026-06-21T12:47:57Z
dc.title.none.fl_str_mv	Hematopoiesis under telomere attrition at the single-cell resolution
title	Hematopoiesis under telomere attrition at the single-cell resolution
spellingShingle	Hematopoiesis under telomere attrition at the single-cell resolution Thongon, N. (Natthakan)\|\|\|/items/514e85a7-885f-4b16-a604-764b22dcefa5 molecular mechanisms hematopoietic stem cell functional decline single-cell technologies
title_short	Hematopoiesis under telomere attrition at the single-cell resolution
title_full	Hematopoiesis under telomere attrition at the single-cell resolution
title_fullStr	Hematopoiesis under telomere attrition at the single-cell resolution
title_full_unstemmed	Hematopoiesis under telomere attrition at the single-cell resolution
title_sort	Hematopoiesis under telomere attrition at the single-cell resolution
dc.creator.none.fl_str_mv	Thongon, N. (Natthakan)\|\|\|/items/514e85a7-885f-4b16-a604-764b22dcefa5 Ma, F. (Feiyang)\|\|\|/items/7ede2a67-0437-4766-9856-d9155d1c854c Santoni, A. (Andrea)\|\|\|/items/d547cac2-df37-441e-b1ac-37766435e274 Marchesini, M. (Matteo)\|\|\|/items/a316eef8-b4b4-4e35-8cd8-37e19fa17d35 Fiorini, E. (Elena)\|\|\|/items/7d56cffc-1272-4194-b43b-ea86cf9f7a72 Rose, A. (Ashley)\|\|\|/items/9d1d6da5-6f11-4d48-853f-5ca8b9bf0e51 Adema, V. (Vera)\|\|\|/items/08bca88e-5689-472d-87e8-4c5e1deafdf3 Gañán-Gómez, I. (Irene)\|\|\|/items/92d1787d-8a7f-414a-af8a-a0cc2094a8af Groarke, E.M. (Emma M.)\|\|\|/items/31a9e9a4-160c-4855-912e-5aef460d67fe Gutiérrez-Rodrigues, F. (Fernanda)\|\|\|/items/153ead07-eab7-4d54-89a5-342692717984 Chen, S. (Shuaitong)\|\|\|/items/1e824da5-11e2-4486-9d90-80b38cb404ef Lockyer, P. (Pamela)\|\|\|/items/69f07a1c-2641-43a7-a665-4dedefefcd41 Schneider, S. (Sarah)\|\|\|/items/6d46d5a8-7d75-456d-8c8d-3f363830dfd8 Bueso-Ramos, C. (Carlos)\|\|\|/items/b7083c64-9627-4e7b-a6ba-3364acb2fa21 Montalbán-Bravo, G. (Guillermo)\|\|\|/items/e911736a-66b9-4e64-9d5c-4475f6a6e61b Class, C.A. (Caleb A.)\|\|\|/items/4294f0fc-a5bd-4a32-b316-06eef51d3d1b Soltysiak, K.A. (Kelly A.)\|\|\|/items/a9cf551e-ccfe-4c48-88dd-d7d4df9bbc1f Pellegrini, M.M. (Massimiliano Matteo)\|\|\|/items/b2629cd3-e142-4554-94fe-f9b652fb06fe Sahin, E. (Ergun)\|\|\|/items/a1432990-ae1a-431e-80fe-4f13ee56367e Bertuch, A.A. (Alison A.)\|\|\|/items/029fdb38-dcf8-4e2b-b836-de42d5dbba2b DiNardo, C.D. (Courtney D.)\|\|\|/items/b7fb579c-78d6-47b0-b007-d1b9e2170587 Garcia-Manero, G. (Guillermo)\|\|\|/items/e2797ef5-c469-437c-afb3-e178412217ce Young, N.S. (Neal S.)\|\|\|/items/764eec3c-5bff-48ad-b4ec-1ae3492c7339 Dwyer, K. (Karen)\|\|\|/items/6a9f7805-c16f-4030-9ad1-ac71d3c360ad Colla, S. (Simona)\|\|\|/items/659f9e93-5695-4c4a-948e-85565d696acc
author	Thongon, N. (Natthakan)\|\|\|/items/514e85a7-885f-4b16-a604-764b22dcefa5
author_facet	Thongon, N. (Natthakan)\|\|\|/items/514e85a7-885f-4b16-a604-764b22dcefa5 Ma, F. (Feiyang)\|\|\|/items/7ede2a67-0437-4766-9856-d9155d1c854c Santoni, A. (Andrea)\|\|\|/items/d547cac2-df37-441e-b1ac-37766435e274 Marchesini, M. (Matteo)\|\|\|/items/a316eef8-b4b4-4e35-8cd8-37e19fa17d35 Fiorini, E. (Elena)\|\|\|/items/7d56cffc-1272-4194-b43b-ea86cf9f7a72 Rose, A. (Ashley)\|\|\|/items/9d1d6da5-6f11-4d48-853f-5ca8b9bf0e51 Adema, V. (Vera)\|\|\|/items/08bca88e-5689-472d-87e8-4c5e1deafdf3 Gañán-Gómez, I. (Irene)\|\|\|/items/92d1787d-8a7f-414a-af8a-a0cc2094a8af Groarke, E.M. (Emma M.)\|\|\|/items/31a9e9a4-160c-4855-912e-5aef460d67fe Gutiérrez-Rodrigues, F. (Fernanda)\|\|\|/items/153ead07-eab7-4d54-89a5-342692717984 Chen, S. (Shuaitong)\|\|\|/items/1e824da5-11e2-4486-9d90-80b38cb404ef Lockyer, P. (Pamela)\|\|\|/items/69f07a1c-2641-43a7-a665-4dedefefcd41 Schneider, S. (Sarah)\|\|\|/items/6d46d5a8-7d75-456d-8c8d-3f363830dfd8 Bueso-Ramos, C. (Carlos)\|\|\|/items/b7083c64-9627-4e7b-a6ba-3364acb2fa21 Montalbán-Bravo, G. (Guillermo)\|\|\|/items/e911736a-66b9-4e64-9d5c-4475f6a6e61b Class, C.A. (Caleb A.)\|\|\|/items/4294f0fc-a5bd-4a32-b316-06eef51d3d1b Soltysiak, K.A. (Kelly A.)\|\|\|/items/a9cf551e-ccfe-4c48-88dd-d7d4df9bbc1f Pellegrini, M.M. (Massimiliano Matteo)\|\|\|/items/b2629cd3-e142-4554-94fe-f9b652fb06fe Sahin, E. (Ergun)\|\|\|/items/a1432990-ae1a-431e-80fe-4f13ee56367e Bertuch, A.A. (Alison A.)\|\|\|/items/029fdb38-dcf8-4e2b-b836-de42d5dbba2b DiNardo, C.D. (Courtney D.)\|\|\|/items/b7fb579c-78d6-47b0-b007-d1b9e2170587 Garcia-Manero, G. (Guillermo)\|\|\|/items/e2797ef5-c469-437c-afb3-e178412217ce Young, N.S. (Neal S.)\|\|\|/items/764eec3c-5bff-48ad-b4ec-1ae3492c7339 Dwyer, K. (Karen)\|\|\|/items/6a9f7805-c16f-4030-9ad1-ac71d3c360ad Colla, S. (Simona)\|\|\|/items/659f9e93-5695-4c4a-948e-85565d696acc
author_role	author
author2	Ma, F. (Feiyang)\|\|\|/items/7ede2a67-0437-4766-9856-d9155d1c854c Santoni, A. (Andrea)\|\|\|/items/d547cac2-df37-441e-b1ac-37766435e274 Marchesini, M. (Matteo)\|\|\|/items/a316eef8-b4b4-4e35-8cd8-37e19fa17d35 Fiorini, E. (Elena)\|\|\|/items/7d56cffc-1272-4194-b43b-ea86cf9f7a72 Rose, A. (Ashley)\|\|\|/items/9d1d6da5-6f11-4d48-853f-5ca8b9bf0e51 Adema, V. (Vera)\|\|\|/items/08bca88e-5689-472d-87e8-4c5e1deafdf3 Gañán-Gómez, I. (Irene)\|\|\|/items/92d1787d-8a7f-414a-af8a-a0cc2094a8af Groarke, E.M. (Emma M.)\|\|\|/items/31a9e9a4-160c-4855-912e-5aef460d67fe Gutiérrez-Rodrigues, F. (Fernanda)\|\|\|/items/153ead07-eab7-4d54-89a5-342692717984 Chen, S. (Shuaitong)\|\|\|/items/1e824da5-11e2-4486-9d90-80b38cb404ef Lockyer, P. (Pamela)\|\|\|/items/69f07a1c-2641-43a7-a665-4dedefefcd41 Schneider, S. (Sarah)\|\|\|/items/6d46d5a8-7d75-456d-8c8d-3f363830dfd8 Bueso-Ramos, C. (Carlos)\|\|\|/items/b7083c64-9627-4e7b-a6ba-3364acb2fa21 Montalbán-Bravo, G. (Guillermo)\|\|\|/items/e911736a-66b9-4e64-9d5c-4475f6a6e61b Class, C.A. (Caleb A.)\|\|\|/items/4294f0fc-a5bd-4a32-b316-06eef51d3d1b Soltysiak, K.A. (Kelly A.)\|\|\|/items/a9cf551e-ccfe-4c48-88dd-d7d4df9bbc1f Pellegrini, M.M. (Massimiliano Matteo)\|\|\|/items/b2629cd3-e142-4554-94fe-f9b652fb06fe Sahin, E. (Ergun)\|\|\|/items/a1432990-ae1a-431e-80fe-4f13ee56367e Bertuch, A.A. (Alison A.)\|\|\|/items/029fdb38-dcf8-4e2b-b836-de42d5dbba2b DiNardo, C.D. (Courtney D.)\|\|\|/items/b7fb579c-78d6-47b0-b007-d1b9e2170587 Garcia-Manero, G. (Guillermo)\|\|\|/items/e2797ef5-c469-437c-afb3-e178412217ce Young, N.S. (Neal S.)\|\|\|/items/764eec3c-5bff-48ad-b4ec-1ae3492c7339 Dwyer, K. (Karen)\|\|\|/items/6a9f7805-c16f-4030-9ad1-ac71d3c360ad Colla, S. (Simona)\|\|\|/items/659f9e93-5695-4c4a-948e-85565d696acc
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Dadun. Depósito Académico Digital Universidad de Navarra
dc.subject.none.fl_str_mv	molecular mechanisms hematopoietic stem cell functional decline single-cell technologies
topic	molecular mechanisms hematopoietic stem cell functional decline single-cell technologies
description	The molecular mechanisms that drive hematopoietic stem cell functional decline under conditions of telomere shortening are not completely understood. In light of recent advances in single-cell technologies, we sought to redefine the transcriptional and epigenetic landscape of mouse and human hematopoietic stem cells under telomere attrition, as induced by pathogenic germline variants in telomerase complex genes. Here, we show that telomere attrition maintains hematopoietic stem cells under persistent metabolic activation and differentiation towards the megakaryocytic lineage through the cell-intrinsic upregulation of the innate immune signaling response, which directly compromises hematopoietic stem cells’ self-renewal capabilities and eventually leads to their exhaustion. Mechanistically, we demonstrate that targeting members of the Ifi20x/IFI16 family of cytosolic DNA sensors using the oligodeoxynucleotide A151, which comprises four repeats of the TTAGGG motif of the telomeric DNA, overcomes interferon signaling activation in telomere-dysfunctional hematopoietic stem cells and these cells’ skewed differentiation towards the megakaryocytic lineage. This study challenges the historical hypothesis that telomere attrition limits the proliferative potential of hematopoietic stem cells by inducing apoptosis, autophagy, or senescence, and suggests that targeting IFI16 signaling axis might prevent hematopoietic stem cell functional decline in conditions affecting telomere maintenance.
publishDate	2021
dc.date.none.fl_str_mv	2021 2021-01-01 2021 2021-01-01
dc.type.none.fl_str_mv	journal article http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://hdl.handle.net/10171/121384
url	https://hdl.handle.net/10171/121384
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	Nature
publisher.none.fl_str_mv	Nature
dc.source.none.fl_str_mv	reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra
instname_str	Universidad de Navarra
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Hematopoiesis under telomere attrition at the single-cell resolution

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