The transcription factor DDIT3 is a potential driver of dyserythropoiesis in myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are hematopoietic stem cell (HSC) malignancies characterized by ineffective hematopoiesis, with increased incidence in older individuals. Here we analyze the transcriptome of human HSCs purified from young and older healthy adults, as well asMDS patients, identifying...

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Authors: Berastegui, Nerea, Ainciburu, Marina, Romero, Juan P., Garcia-Olloqui, Paula, Alfonso-Pierola, Ana, Philippe, Céline, Vilas-Zornoza, Amaia, San Martin-Uriz, Patxi, Ruiz-Hernández, Raquel, Abarrategi, Ander, Ordoñez, Raquel, Alignani, Diego, Sarvide, Sarai, Castro-Labrador, Laura, Lamo de Espinosa Vázquez de Sola, José María, San‑Julián, Mikel, Jimenez, Tamara, López Cadenas, Félix, Muntion, Sandra, Sanchez-Guijo, Fermín, Molero, Antonieta, Montoro, Julia
Format: article
Publication Date:2022
Country:España
Institution:Universidad Católica de Valencia San Vicente Mártir
Repository:RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
Language:English
OAI Identifier:oai:riucv.ucv.es:20.500.12466/5216
Online Access:http://hdl.handle.net/20.500.12466/5216
Access Level:Open access
Keyword:Ageing
Haematopoietic stem cells
Myelodysplastic syndrome
Transcriptomics
3205.04 Hematología
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oai_identifier_str oai:riucv.ucv.es:20.500.12466/5216
network_acronym_str ES
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spelling The transcription factor DDIT3 is a potential driver of dyserythropoiesis in myelodysplastic syndromesBerastegui, NereaAinciburu, MarinaRomero, Juan P.Garcia-Olloqui, PaulaAlfonso-Pierola, AnaPhilippe, CélineVilas-Zornoza, AmaiaSan Martin-Uriz, PatxiRuiz-Hernández, RaquelAbarrategi, AnderOrdoñez, RaquelAlignani, DiegoSarvide, SaraiCastro-Labrador, LauraLamo de Espinosa Vázquez de Sola, José MaríaSan‑Julián, MikelJimenez, TamaraLópez Cadenas, FélixMuntion, SandraSanchez-Guijo, FermínMolero, AntonietaMontoro, JuliaAgeingHaematopoietic stem cellsMyelodysplastic syndromeTranscriptomics3205.04 HematologíaMyelodysplastic syndromes (MDS) are hematopoietic stem cell (HSC) malignancies characterized by ineffective hematopoiesis, with increased incidence in older individuals. Here we analyze the transcriptome of human HSCs purified from young and older healthy adults, as well asMDS patients, identifying transcriptional alterations following different patterns of expression. While aging-associated lesions seem to predispose HSCs to myeloid transformation, disease-specific alterations may trigger MDS development. Among MDSspecific lesions, we detect the upregulation of the transcription factor DNA Damage Inducible Transcript 3 (DDIT3). Overexpression of DDIT3 in human healthyHSCs induces anMDS-like transcriptional state, and dyserythropoiesis, an effect associated with a failure in the activation of transcriptional programs required for normal erythroid differentiation. Moreover, DDIT3 knockdown in CD34+ cells from MDS patients with anemia is able to restore erythropoiesis. These results identify DDIT3 as a driver of dyserythropoiesis, and a potential therapeutic target to restore the inefficient erythroid differentiation characterizing MDS patients.20252025-01-2020222022-12-0120222022-12-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12466/5216reponame:RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártirinstname:Universidad Católica de Valencia San Vicente MártirInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:riucv.ucv.es:20.500.12466/52162026-06-19T08:32:07Z
dc.title.none.fl_str_mv The transcription factor DDIT3 is a potential driver of dyserythropoiesis in myelodysplastic syndromes
title The transcription factor DDIT3 is a potential driver of dyserythropoiesis in myelodysplastic syndromes
spellingShingle The transcription factor DDIT3 is a potential driver of dyserythropoiesis in myelodysplastic syndromes
Berastegui, Nerea
Ageing
Haematopoietic stem cells
Myelodysplastic syndrome
Transcriptomics
3205.04 Hematología
title_short The transcription factor DDIT3 is a potential driver of dyserythropoiesis in myelodysplastic syndromes
title_full The transcription factor DDIT3 is a potential driver of dyserythropoiesis in myelodysplastic syndromes
title_fullStr The transcription factor DDIT3 is a potential driver of dyserythropoiesis in myelodysplastic syndromes
title_full_unstemmed The transcription factor DDIT3 is a potential driver of dyserythropoiesis in myelodysplastic syndromes
title_sort The transcription factor DDIT3 is a potential driver of dyserythropoiesis in myelodysplastic syndromes
dc.creator.none.fl_str_mv Berastegui, Nerea
Ainciburu, Marina
Romero, Juan P.
Garcia-Olloqui, Paula
Alfonso-Pierola, Ana
Philippe, Céline
Vilas-Zornoza, Amaia
San Martin-Uriz, Patxi
Ruiz-Hernández, Raquel
Abarrategi, Ander
Ordoñez, Raquel
Alignani, Diego
Sarvide, Sarai
Castro-Labrador, Laura
Lamo de Espinosa Vázquez de Sola, José María
San‑Julián, Mikel
Jimenez, Tamara
López Cadenas, Félix
Muntion, Sandra
Sanchez-Guijo, Fermín
Molero, Antonieta
Montoro, Julia
author Berastegui, Nerea
author_facet Berastegui, Nerea
Ainciburu, Marina
Romero, Juan P.
Garcia-Olloqui, Paula
Alfonso-Pierola, Ana
Philippe, Céline
Vilas-Zornoza, Amaia
San Martin-Uriz, Patxi
Ruiz-Hernández, Raquel
Abarrategi, Ander
Ordoñez, Raquel
Alignani, Diego
Sarvide, Sarai
Castro-Labrador, Laura
Lamo de Espinosa Vázquez de Sola, José María
San‑Julián, Mikel
Jimenez, Tamara
López Cadenas, Félix
Muntion, Sandra
Sanchez-Guijo, Fermín
Molero, Antonieta
Montoro, Julia
author_role author
author2 Ainciburu, Marina
Romero, Juan P.
Garcia-Olloqui, Paula
Alfonso-Pierola, Ana
Philippe, Céline
Vilas-Zornoza, Amaia
San Martin-Uriz, Patxi
Ruiz-Hernández, Raquel
Abarrategi, Ander
Ordoñez, Raquel
Alignani, Diego
Sarvide, Sarai
Castro-Labrador, Laura
Lamo de Espinosa Vázquez de Sola, José María
San‑Julián, Mikel
Jimenez, Tamara
López Cadenas, Félix
Muntion, Sandra
Sanchez-Guijo, Fermín
Molero, Antonieta
Montoro, Julia
author2_role 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
dc.subject.none.fl_str_mv Ageing
Haematopoietic stem cells
Myelodysplastic syndrome
Transcriptomics
3205.04 Hematología
topic Ageing
Haematopoietic stem cells
Myelodysplastic syndrome
Transcriptomics
3205.04 Hematología
description Myelodysplastic syndromes (MDS) are hematopoietic stem cell (HSC) malignancies characterized by ineffective hematopoiesis, with increased incidence in older individuals. Here we analyze the transcriptome of human HSCs purified from young and older healthy adults, as well asMDS patients, identifying transcriptional alterations following different patterns of expression. While aging-associated lesions seem to predispose HSCs to myeloid transformation, disease-specific alterations may trigger MDS development. Among MDSspecific lesions, we detect the upregulation of the transcription factor DNA Damage Inducible Transcript 3 (DDIT3). Overexpression of DDIT3 in human healthyHSCs induces anMDS-like transcriptional state, and dyserythropoiesis, an effect associated with a failure in the activation of transcriptional programs required for normal erythroid differentiation. Moreover, DDIT3 knockdown in CD34+ cells from MDS patients with anemia is able to restore erythropoiesis. These results identify DDIT3 as a driver of dyserythropoiesis, and a potential therapeutic target to restore the inefficient erythroid differentiation characterizing MDS patients.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-12-01
2022
2022-12-01
2025
2025-01-20
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12466/5216
url http://hdl.handle.net/20.500.12466/5216
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
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
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
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
instname:Universidad Católica de Valencia San Vicente Mártir
instname_str Universidad Católica de Valencia San Vicente Mártir
reponame_str RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
collection RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,228081

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