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

Berastegui-Zufiaurre, N. (Nerea)|||/items/a609b1d4-fbed-4852-96eb-90e1cfe04e52; Ainciburu-Fernández, M. (Marina)|||/items/71018cd2-9706-4dd0-84a9-77a8d03fef99; Romero, J.P. (Juan Pablo)|||/items/03616479-3ca5-416f-9f44-f57c64007d00; García-Olloqui, P. (Paula)|||/items/33aebcca-bf96-4a81-a74d-9fcd60b275cc; Alfonso-Piérola, A. (Ana)|||/items/0212a5e6-923f-42aa-8ba3-b0ce4e1d6e10; Philippe, C. (Céline)|||/items/7c97d9fe-4c30-4dbf-b39f-595598b9e15c; Vilas-Zornoza, A. (Amaia)|||/items/7435672d-e471-4409-8325-006fef27fb12; San-Martín-Uriz, P. (Patxi)|||/items/621b7a74-311b-4ff1-b688-53d810e30429; Ruiz-Hernández, R. (Raquel)|||/items/e0401d53-1484-4dc0-8b0d-f1abb02db78f; Abarrategi, A. (Ander)|||/items/66fa1ab7-d0b0-40fc-9af3-df82e6161276; Ordoñez, R. (Raquel)|||/items/0c912257-4c28-4c5b-9992-04a581a906cf; Alignani, D.O. (Diego Óscar)|||/items/86bf2300-6dd0-46b3-90d9-270da3841ff0; Sarvide, S. (Sarai)|||/items/778fe9e0-6619-4699-ac88-8b1f43f83e98; Castro-Labrador, L. (Laura)|||/items/1ce49365-a8f0-4160-84f8-ebf2535f4b50; Lamo-de-Espinosa-Vázquez-de-Sola, J.M. (José María)|||/items/75feb837-6d53-41fe-808d-4b70661db44e; San-Julian-Aranguren, M. (Mikel)|||/items/6e7e8dd2-8377-4055-a88e-809615df92e3; Jimenez-Solas, T. (Tamara)|||/items/7a4dbe5e-7060-4c1d-b632-9dd5089fe072; Lopez-Cadenas, F. (Félix)|||/items/08bd9f83-210a-4e48-90c5-c8ed57694aed; Muntion, S. (Sandra)|||/items/0f21eed5-2617-445a-b325-c69361e39a06; Sanchez-Guijo, F.M. (Fermín M.)|||/items/b31fe6cf-bc6a-42fb-8a92-116c4f62dd49; Molero, A. (Antonieta)|||/items/ea2d4363-f7f8-4859-b4f8-bf034d96ed9e; Montoro-Gómez, M.J. (Maria Julia)|||/items/9bd28e22-a47c-43ed-9001-e3e5c95aebec; Tazón-Vega, Bárbara|||/items/615e5185-c87e-4883-a0b2-2634cfa12c6c; Serrano-Sanz, G. (Guillermo)|||/items/5ed5047b-1ad7-44a2-8674-de750c97b7c5; Díaz-Mazkiaran, A. (Aintzane)|||/items/8f723f6e-3569-43c9-ae70-07499bc3cac8; Hernaez-Arrazola, M. (Mikel)|||/items/954a4ee7-b04c-4dc5-9bfc-7a48332c7e5a; Huerga-Dominguez, S. (Sofia)|||/items/a62c6e59-be71-4b34-b0b6-6deb286bbf3f; Bewicke-Copley, F. (Findlay)|||/items/845f2094-1595-4b42-b77c-ebc1fb40c33a; Rio-Machin, A. (Ana)|||/items/65fc3307-4197-4308-b9e6-688d8108df08; Maurano, M.T. (Matthew T.)|||/items/6a16f90a-a187-48bf-a77c-d623aaf85ab5

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 as MDS patients, identifying...

Descripción completa

Detalles Bibliográficos
Autores:	Berastegui-Zufiaurre, N. (Nerea)\|\|\|/items/a609b1d4-fbed-4852-96eb-90e1cfe04e52, Ainciburu-Fernández, M. (Marina)\|\|\|/items/71018cd2-9706-4dd0-84a9-77a8d03fef99, Romero, J.P. (Juan Pablo)\|\|\|/items/03616479-3ca5-416f-9f44-f57c64007d00, García-Olloqui, P. (Paula)\|\|\|/items/33aebcca-bf96-4a81-a74d-9fcd60b275cc, Alfonso-Piérola, A. (Ana)\|\|\|/items/0212a5e6-923f-42aa-8ba3-b0ce4e1d6e10, Philippe, C. (Céline)\|\|\|/items/7c97d9fe-4c30-4dbf-b39f-595598b9e15c, Vilas-Zornoza, A. (Amaia)\|\|\|/items/7435672d-e471-4409-8325-006fef27fb12, San-Martín-Uriz, P. (Patxi)\|\|\|/items/621b7a74-311b-4ff1-b688-53d810e30429, Ruiz-Hernández, R. (Raquel)\|\|\|/items/e0401d53-1484-4dc0-8b0d-f1abb02db78f, Abarrategi, A. (Ander)\|\|\|/items/66fa1ab7-d0b0-40fc-9af3-df82e6161276, Ordoñez, R. (Raquel)\|\|\|/items/0c912257-4c28-4c5b-9992-04a581a906cf, Alignani, D.O. (Diego Óscar)\|\|\|/items/86bf2300-6dd0-46b3-90d9-270da3841ff0, Sarvide, S. (Sarai)\|\|\|/items/778fe9e0-6619-4699-ac88-8b1f43f83e98, Castro-Labrador, L. (Laura)\|\|\|/items/1ce49365-a8f0-4160-84f8-ebf2535f4b50, Lamo-de-Espinosa-Vázquez-de-Sola, J.M. (José María)\|\|\|/items/75feb837-6d53-41fe-808d-4b70661db44e, San-Julian-Aranguren, M. (Mikel)\|\|\|/items/6e7e8dd2-8377-4055-a88e-809615df92e3, Jimenez-Solas, T. (Tamara)\|\|\|/items/7a4dbe5e-7060-4c1d-b632-9dd5089fe072, Lopez-Cadenas, F. (Félix)\|\|\|/items/08bd9f83-210a-4e48-90c5-c8ed57694aed, Muntion, S. (Sandra)\|\|\|/items/0f21eed5-2617-445a-b325-c69361e39a06, Sanchez-Guijo, F.M. (Fermín M.)\|\|\|/items/b31fe6cf-bc6a-42fb-8a92-116c4f62dd49, Molero, A. (Antonieta)\|\|\|/items/ea2d4363-f7f8-4859-b4f8-bf034d96ed9e, Montoro-Gómez, M.J. (Maria Julia)\|\|\|/items/9bd28e22-a47c-43ed-9001-e3e5c95aebec, Tazón-Vega, Bárbara\|\|\|/items/615e5185-c87e-4883-a0b2-2634cfa12c6c, Serrano-Sanz, G. (Guillermo)\|\|\|/items/5ed5047b-1ad7-44a2-8674-de750c97b7c5, Díaz-Mazkiaran, A. (Aintzane)\|\|\|/items/8f723f6e-3569-43c9-ae70-07499bc3cac8, Hernaez-Arrazola, M. (Mikel)\|\|\|/items/954a4ee7-b04c-4dc5-9bfc-7a48332c7e5a, Huerga-Dominguez, S. (Sofia)\|\|\|/items/a62c6e59-be71-4b34-b0b6-6deb286bbf3f, Bewicke-Copley, F. (Findlay)\|\|\|/items/845f2094-1595-4b42-b77c-ebc1fb40c33a, Rio-Machin, A. (Ana)\|\|\|/items/65fc3307-4197-4308-b9e6-688d8108df08, Maurano, M.T. (Matthew T.)\|\|\|/items/6a16f90a-a187-48bf-a77c-d623aaf85ab5
Tipo de recurso:	artículo
Fecha de publicación:	2022
País:	España
Institución:	Universidad de Navarra
Repositorio:	Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:	inglés
OAI Identifier:	oai:dadun.unav.edu:10171/113419
Acceso en línea:	https://hdl.handle.net/10171/113419
Access Level:	acceso abierto

id	ES_fceb45f0cd355f71244d70159745b1bc
oai_identifier_str	oai:dadun.unav.edu:10171/113419
network_acronym_str	ES
network_name_str	España
repository_id_str
spelling	The transcription factor DDIT3 is a potential driver of dyserythropoiesis in myelodysplastic syndromesBerastegui-Zufiaurre, N. (Nerea)\|\|\|/items/a609b1d4-fbed-4852-96eb-90e1cfe04e52Ainciburu-Fernández, M. (Marina)\|\|\|/items/71018cd2-9706-4dd0-84a9-77a8d03fef99Romero, J.P. (Juan Pablo)\|\|\|/items/03616479-3ca5-416f-9f44-f57c64007d00García-Olloqui, P. (Paula)\|\|\|/items/33aebcca-bf96-4a81-a74d-9fcd60b275ccAlfonso-Piérola, A. (Ana)\|\|\|/items/0212a5e6-923f-42aa-8ba3-b0ce4e1d6e10Philippe, C. (Céline)\|\|\|/items/7c97d9fe-4c30-4dbf-b39f-595598b9e15cVilas-Zornoza, A. (Amaia)\|\|\|/items/7435672d-e471-4409-8325-006fef27fb12San-Martín-Uriz, P. (Patxi)\|\|\|/items/621b7a74-311b-4ff1-b688-53d810e30429Ruiz-Hernández, R. (Raquel)\|\|\|/items/e0401d53-1484-4dc0-8b0d-f1abb02db78fAbarrategi, A. (Ander)\|\|\|/items/66fa1ab7-d0b0-40fc-9af3-df82e6161276Ordoñez, R. (Raquel)\|\|\|/items/0c912257-4c28-4c5b-9992-04a581a906cfAlignani, D.O. (Diego Óscar)\|\|\|/items/86bf2300-6dd0-46b3-90d9-270da3841ff0Sarvide, S. (Sarai)\|\|\|/items/778fe9e0-6619-4699-ac88-8b1f43f83e98Castro-Labrador, L. (Laura)\|\|\|/items/1ce49365-a8f0-4160-84f8-ebf2535f4b50Lamo-de-Espinosa-Vázquez-de-Sola, J.M. (José María)\|\|\|/items/75feb837-6d53-41fe-808d-4b70661db44eSan-Julian-Aranguren, M. (Mikel)\|\|\|/items/6e7e8dd2-8377-4055-a88e-809615df92e3Jimenez-Solas, T. (Tamara)\|\|\|/items/7a4dbe5e-7060-4c1d-b632-9dd5089fe072Lopez-Cadenas, F. (Félix)\|\|\|/items/08bd9f83-210a-4e48-90c5-c8ed57694aedMuntion, S. (Sandra)\|\|\|/items/0f21eed5-2617-445a-b325-c69361e39a06Sanchez-Guijo, F.M. (Fermín M.)\|\|\|/items/b31fe6cf-bc6a-42fb-8a92-116c4f62dd49Molero, A. (Antonieta)\|\|\|/items/ea2d4363-f7f8-4859-b4f8-bf034d96ed9eMontoro-Gómez, M.J. (Maria Julia)\|\|\|/items/9bd28e22-a47c-43ed-9001-e3e5c95aebecTazón-Vega, Bárbara\|\|\|/items/615e5185-c87e-4883-a0b2-2634cfa12c6cSerrano-Sanz, G. (Guillermo)\|\|\|/items/5ed5047b-1ad7-44a2-8674-de750c97b7c5Díaz-Mazkiaran, A. (Aintzane)\|\|\|/items/8f723f6e-3569-43c9-ae70-07499bc3cac8Hernaez-Arrazola, M. (Mikel)\|\|\|/items/954a4ee7-b04c-4dc5-9bfc-7a48332c7e5aHuerga-Dominguez, S. (Sofia)\|\|\|/items/a62c6e59-be71-4b34-b0b6-6deb286bbf3fBewicke-Copley, F. (Findlay)\|\|\|/items/845f2094-1595-4b42-b77c-ebc1fb40c33aRio-Machin, A. (Ana)\|\|\|/items/65fc3307-4197-4308-b9e6-688d8108df08Maurano, M.T. (Matthew T.)\|\|\|/items/6a16f90a-a187-48bf-a77c-d623aaf85ab5Myelodysplastic 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 as MDS 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 MDS-specific lesions, we detect the upregulation of the transcription factor DNA Damage Inducible Transcript 3 (DDIT3). Overexpression of DDIT3 in human healthy HSCs induces an MDS-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.Nature ResearchDadun. Depósito Académico Digital Universidad de Navarra20222022-01-0120222022-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/113419reponame: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:10171/1134192026-06-21T12:47:57Z
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-Zufiaurre, N. (Nerea)\|\|\|/items/a609b1d4-fbed-4852-96eb-90e1cfe04e52
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-Zufiaurre, N. (Nerea)\|\|\|/items/a609b1d4-fbed-4852-96eb-90e1cfe04e52 Ainciburu-Fernández, M. (Marina)\|\|\|/items/71018cd2-9706-4dd0-84a9-77a8d03fef99 Romero, J.P. (Juan Pablo)\|\|\|/items/03616479-3ca5-416f-9f44-f57c64007d00 García-Olloqui, P. (Paula)\|\|\|/items/33aebcca-bf96-4a81-a74d-9fcd60b275cc Alfonso-Piérola, A. (Ana)\|\|\|/items/0212a5e6-923f-42aa-8ba3-b0ce4e1d6e10 Philippe, C. (Céline)\|\|\|/items/7c97d9fe-4c30-4dbf-b39f-595598b9e15c Vilas-Zornoza, A. (Amaia)\|\|\|/items/7435672d-e471-4409-8325-006fef27fb12 San-Martín-Uriz, P. (Patxi)\|\|\|/items/621b7a74-311b-4ff1-b688-53d810e30429 Ruiz-Hernández, R. (Raquel)\|\|\|/items/e0401d53-1484-4dc0-8b0d-f1abb02db78f Abarrategi, A. (Ander)\|\|\|/items/66fa1ab7-d0b0-40fc-9af3-df82e6161276 Ordoñez, R. (Raquel)\|\|\|/items/0c912257-4c28-4c5b-9992-04a581a906cf Alignani, D.O. (Diego Óscar)\|\|\|/items/86bf2300-6dd0-46b3-90d9-270da3841ff0 Sarvide, S. (Sarai)\|\|\|/items/778fe9e0-6619-4699-ac88-8b1f43f83e98 Castro-Labrador, L. (Laura)\|\|\|/items/1ce49365-a8f0-4160-84f8-ebf2535f4b50 Lamo-de-Espinosa-Vázquez-de-Sola, J.M. (José María)\|\|\|/items/75feb837-6d53-41fe-808d-4b70661db44e San-Julian-Aranguren, M. (Mikel)\|\|\|/items/6e7e8dd2-8377-4055-a88e-809615df92e3 Jimenez-Solas, T. (Tamara)\|\|\|/items/7a4dbe5e-7060-4c1d-b632-9dd5089fe072 Lopez-Cadenas, F. (Félix)\|\|\|/items/08bd9f83-210a-4e48-90c5-c8ed57694aed Muntion, S. (Sandra)\|\|\|/items/0f21eed5-2617-445a-b325-c69361e39a06 Sanchez-Guijo, F.M. (Fermín M.)\|\|\|/items/b31fe6cf-bc6a-42fb-8a92-116c4f62dd49 Molero, A. (Antonieta)\|\|\|/items/ea2d4363-f7f8-4859-b4f8-bf034d96ed9e Montoro-Gómez, M.J. (Maria Julia)\|\|\|/items/9bd28e22-a47c-43ed-9001-e3e5c95aebec Tazón-Vega, Bárbara\|\|\|/items/615e5185-c87e-4883-a0b2-2634cfa12c6c Serrano-Sanz, G. (Guillermo)\|\|\|/items/5ed5047b-1ad7-44a2-8674-de750c97b7c5 Díaz-Mazkiaran, A. (Aintzane)\|\|\|/items/8f723f6e-3569-43c9-ae70-07499bc3cac8 Hernaez-Arrazola, M. (Mikel)\|\|\|/items/954a4ee7-b04c-4dc5-9bfc-7a48332c7e5a Huerga-Dominguez, S. (Sofia)\|\|\|/items/a62c6e59-be71-4b34-b0b6-6deb286bbf3f Bewicke-Copley, F. (Findlay)\|\|\|/items/845f2094-1595-4b42-b77c-ebc1fb40c33a Rio-Machin, A. (Ana)\|\|\|/items/65fc3307-4197-4308-b9e6-688d8108df08 Maurano, M.T. (Matthew T.)\|\|\|/items/6a16f90a-a187-48bf-a77c-d623aaf85ab5
author	Berastegui-Zufiaurre, N. (Nerea)\|\|\|/items/a609b1d4-fbed-4852-96eb-90e1cfe04e52
author_facet	Berastegui-Zufiaurre, N. (Nerea)\|\|\|/items/a609b1d4-fbed-4852-96eb-90e1cfe04e52 Ainciburu-Fernández, M. (Marina)\|\|\|/items/71018cd2-9706-4dd0-84a9-77a8d03fef99 Romero, J.P. (Juan Pablo)\|\|\|/items/03616479-3ca5-416f-9f44-f57c64007d00 García-Olloqui, P. (Paula)\|\|\|/items/33aebcca-bf96-4a81-a74d-9fcd60b275cc Alfonso-Piérola, A. (Ana)\|\|\|/items/0212a5e6-923f-42aa-8ba3-b0ce4e1d6e10 Philippe, C. (Céline)\|\|\|/items/7c97d9fe-4c30-4dbf-b39f-595598b9e15c Vilas-Zornoza, A. (Amaia)\|\|\|/items/7435672d-e471-4409-8325-006fef27fb12 San-Martín-Uriz, P. (Patxi)\|\|\|/items/621b7a74-311b-4ff1-b688-53d810e30429 Ruiz-Hernández, R. (Raquel)\|\|\|/items/e0401d53-1484-4dc0-8b0d-f1abb02db78f Abarrategi, A. (Ander)\|\|\|/items/66fa1ab7-d0b0-40fc-9af3-df82e6161276 Ordoñez, R. (Raquel)\|\|\|/items/0c912257-4c28-4c5b-9992-04a581a906cf Alignani, D.O. (Diego Óscar)\|\|\|/items/86bf2300-6dd0-46b3-90d9-270da3841ff0 Sarvide, S. (Sarai)\|\|\|/items/778fe9e0-6619-4699-ac88-8b1f43f83e98 Castro-Labrador, L. (Laura)\|\|\|/items/1ce49365-a8f0-4160-84f8-ebf2535f4b50 Lamo-de-Espinosa-Vázquez-de-Sola, J.M. (José María)\|\|\|/items/75feb837-6d53-41fe-808d-4b70661db44e San-Julian-Aranguren, M. (Mikel)\|\|\|/items/6e7e8dd2-8377-4055-a88e-809615df92e3 Jimenez-Solas, T. (Tamara)\|\|\|/items/7a4dbe5e-7060-4c1d-b632-9dd5089fe072 Lopez-Cadenas, F. (Félix)\|\|\|/items/08bd9f83-210a-4e48-90c5-c8ed57694aed Muntion, S. (Sandra)\|\|\|/items/0f21eed5-2617-445a-b325-c69361e39a06 Sanchez-Guijo, F.M. (Fermín M.)\|\|\|/items/b31fe6cf-bc6a-42fb-8a92-116c4f62dd49 Molero, A. (Antonieta)\|\|\|/items/ea2d4363-f7f8-4859-b4f8-bf034d96ed9e Montoro-Gómez, M.J. (Maria Julia)\|\|\|/items/9bd28e22-a47c-43ed-9001-e3e5c95aebec Tazón-Vega, Bárbara\|\|\|/items/615e5185-c87e-4883-a0b2-2634cfa12c6c Serrano-Sanz, G. (Guillermo)\|\|\|/items/5ed5047b-1ad7-44a2-8674-de750c97b7c5 Díaz-Mazkiaran, A. (Aintzane)\|\|\|/items/8f723f6e-3569-43c9-ae70-07499bc3cac8 Hernaez-Arrazola, M. (Mikel)\|\|\|/items/954a4ee7-b04c-4dc5-9bfc-7a48332c7e5a Huerga-Dominguez, S. (Sofia)\|\|\|/items/a62c6e59-be71-4b34-b0b6-6deb286bbf3f Bewicke-Copley, F. (Findlay)\|\|\|/items/845f2094-1595-4b42-b77c-ebc1fb40c33a Rio-Machin, A. (Ana)\|\|\|/items/65fc3307-4197-4308-b9e6-688d8108df08 Maurano, M.T. (Matthew T.)\|\|\|/items/6a16f90a-a187-48bf-a77c-d623aaf85ab5
author_role	author
author2	Ainciburu-Fernández, M. (Marina)\|\|\|/items/71018cd2-9706-4dd0-84a9-77a8d03fef99 Romero, J.P. (Juan Pablo)\|\|\|/items/03616479-3ca5-416f-9f44-f57c64007d00 García-Olloqui, P. (Paula)\|\|\|/items/33aebcca-bf96-4a81-a74d-9fcd60b275cc Alfonso-Piérola, A. (Ana)\|\|\|/items/0212a5e6-923f-42aa-8ba3-b0ce4e1d6e10 Philippe, C. (Céline)\|\|\|/items/7c97d9fe-4c30-4dbf-b39f-595598b9e15c Vilas-Zornoza, A. (Amaia)\|\|\|/items/7435672d-e471-4409-8325-006fef27fb12 San-Martín-Uriz, P. (Patxi)\|\|\|/items/621b7a74-311b-4ff1-b688-53d810e30429 Ruiz-Hernández, R. (Raquel)\|\|\|/items/e0401d53-1484-4dc0-8b0d-f1abb02db78f Abarrategi, A. (Ander)\|\|\|/items/66fa1ab7-d0b0-40fc-9af3-df82e6161276 Ordoñez, R. (Raquel)\|\|\|/items/0c912257-4c28-4c5b-9992-04a581a906cf Alignani, D.O. (Diego Óscar)\|\|\|/items/86bf2300-6dd0-46b3-90d9-270da3841ff0 Sarvide, S. (Sarai)\|\|\|/items/778fe9e0-6619-4699-ac88-8b1f43f83e98 Castro-Labrador, L. (Laura)\|\|\|/items/1ce49365-a8f0-4160-84f8-ebf2535f4b50 Lamo-de-Espinosa-Vázquez-de-Sola, J.M. (José María)\|\|\|/items/75feb837-6d53-41fe-808d-4b70661db44e San-Julian-Aranguren, M. (Mikel)\|\|\|/items/6e7e8dd2-8377-4055-a88e-809615df92e3 Jimenez-Solas, T. (Tamara)\|\|\|/items/7a4dbe5e-7060-4c1d-b632-9dd5089fe072 Lopez-Cadenas, F. (Félix)\|\|\|/items/08bd9f83-210a-4e48-90c5-c8ed57694aed Muntion, S. (Sandra)\|\|\|/items/0f21eed5-2617-445a-b325-c69361e39a06 Sanchez-Guijo, F.M. (Fermín M.)\|\|\|/items/b31fe6cf-bc6a-42fb-8a92-116c4f62dd49 Molero, A. (Antonieta)\|\|\|/items/ea2d4363-f7f8-4859-b4f8-bf034d96ed9e Montoro-Gómez, M.J. (Maria Julia)\|\|\|/items/9bd28e22-a47c-43ed-9001-e3e5c95aebec Tazón-Vega, Bárbara\|\|\|/items/615e5185-c87e-4883-a0b2-2634cfa12c6c Serrano-Sanz, G. (Guillermo)\|\|\|/items/5ed5047b-1ad7-44a2-8674-de750c97b7c5 Díaz-Mazkiaran, A. (Aintzane)\|\|\|/items/8f723f6e-3569-43c9-ae70-07499bc3cac8 Hernaez-Arrazola, M. (Mikel)\|\|\|/items/954a4ee7-b04c-4dc5-9bfc-7a48332c7e5a Huerga-Dominguez, S. (Sofia)\|\|\|/items/a62c6e59-be71-4b34-b0b6-6deb286bbf3f Bewicke-Copley, F. (Findlay)\|\|\|/items/845f2094-1595-4b42-b77c-ebc1fb40c33a Rio-Machin, A. (Ana)\|\|\|/items/65fc3307-4197-4308-b9e6-688d8108df08 Maurano, M.T. (Matthew T.)\|\|\|/items/6a16f90a-a187-48bf-a77c-d623aaf85ab5
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 author author author author author
dc.contributor.none.fl_str_mv	Dadun. Depósito Académico Digital Universidad de Navarra
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 as MDS 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 MDS-specific lesions, we detect the upregulation of the transcription factor DNA Damage Inducible Transcript 3 (DDIT3). Overexpression of DDIT3 in human healthy HSCs induces an MDS-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 2022-01-01 2022 2022-01-01
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/10171/113419
url	https://hdl.handle.net/10171/113419
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 Research
publisher.none.fl_str_mv	Nature Research
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
reponame_str	Dadun. Depósito Académico Digital de la Universidad de Navarra
collection	Dadun. Depósito Académico Digital de la Universidad de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_	1869425493269282816
score	15.812429

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

Similares en LA Referencia