Single-cell transcriptional profile of CD34+ hematopoietic progenitor cells from del(5q) myelodysplastic syndromes and impact of lenalidomide
While myelodysplastic syndromes with del(5q) (del(5q) MDS) comprises a well-defined hematological subgroup, the molecular basis underlying its origin remains unknown. Using single cell RNA-seq (scRNA-seq) on CD34+ progenitors from del(5q) MDS patients, we have identified cells harboring the deletion...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/113241 |
| Acceso en línea: | https://hdl.handle.net/10171/113241 |
| Access Level: | acceso abierto |
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Single-cell transcriptional profile of CD34+ hematopoietic progenitor cells from del(5q) myelodysplastic syndromes and impact of lenalidomideSerrano-Sanz, G. (Guillermo)|||/items/5ed5047b-1ad7-44a2-8674-de750c97b7c5Berastegui-Zufiaurre, N. (Nerea)|||/items/a609b1d4-fbed-4852-96eb-90e1cfe04e52Díaz-Mazkiaran, A. (Aintzane)|||/items/8f723f6e-3569-43c9-ae70-07499bc3cac8García-Olloqui, P. (Paula)|||/items/33aebcca-bf96-4a81-a74d-9fcd60b275ccRodriguez-Res, C. (Carmen)|||/items/99683585-e42d-4e7b-8031-93320beed7fdHuerga-Dominguez, S. (Sofia)|||/items/a62c6e59-be71-4b34-b0b6-6deb286bbf3fAinciburu-Fernández, M. (Marina)|||/items/71018cd2-9706-4dd0-84a9-77a8d03fef99Vilas-Zornoza, A. (Amaia)|||/items/7435672d-e471-4409-8325-006fef27fb12San-Martín-Uriz, P. (Patxi)|||/items/621b7a74-311b-4ff1-b688-53d810e30429Aguirre-Ruiz, P. (Paula)|||/items/fd10df63-1585-43c5-bb82-d4357a15e7d8Ullate-Agote, A. (Asier)|||/items/af0561e9-aebe-4e94-9cb1-6bb3aa8bf975Ariceta, B. (Beñat)|||/items/e0060bfb-843a-4b76-a474-b79c0eeec803Lamo-de-Espinosa-Vázquez-de-Sola, J.M. (José María)|||/items/75feb837-6d53-41fe-808d-4b70661db44eAcha, P. (Pamela)|||/items/7d12fe4a-6af1-41ff-8d28-87598f6ca8cbCalvete, O. (Oriol)|||/items/a22ae40f-38fc-4588-ad08-a83629184206Jimenez-Solas, T. (Tamara)|||/items/7a4dbe5e-7060-4c1d-b632-9dd5089fe072Molero, A. (Antonieta)|||/items/ea2d4363-f7f8-4859-b4f8-bf034d96ed9eMontoro-Gómez, M.J. (Maria Julia)|||/items/9bd28e22-a47c-43ed-9001-e3e5c95aebecDiez-Campelo, M. (Maria)|||/items/80adaceb-3fc4-44c2-bba0-2c88e6400317Valcarcel, D. (David)|||/items/672eb58a-39da-45ab-85d2-58b2496cd1abSole, F. (Francisco)|||/items/cb283076-40b1-4363-81ee-5275088886bfAlfonso-Piérola, A. (Ana)|||/items/0212a5e6-923f-42aa-8ba3-b0ce4e1d6e10Prosper-Cardoso, F. (Felipe)|||/items/3d1b0b82-06c3-4e63-8280-e903dc4dc0c1Ezponda-Itoiz, T. (Teresa)|||/items/6941e85c-0814-4cde-9237-84a06fbf1697Hernaez-Arrazola, M. (Mikel)|||/items/954a4ee7-b04c-4dc5-9bfc-7a48332c7e5aOchoa-Álvarez, I. (Idoia)|||/items/6326dacc-419f-4156-a9c3-9e79cfcc6a3cWhile myelodysplastic syndromes with del(5q) (del(5q) MDS) comprises a well-defined hematological subgroup, the molecular basis underlying its origin remains unknown. Using single cell RNA-seq (scRNA-seq) on CD34+ progenitors from del(5q) MDS patients, we have identified cells harboring the deletion, characterizing the transcriptional impact of this genetic insult on disease pathogenesis and treatment response. Interestingly, both del(5q) and non-del(5q) cells present similar transcriptional lesions, indicating that all cells, and not only those harboring the deletion, may contribute to aberrant hematopoietic differentiation. However, gene regulatory network (GRN) analyses reveal a group of regulons showing aberrant activity that could trigger altered hematopoiesis exclusively in del(5q) cells, pointing to a more prominent role of these cells in disease phenotype. In del(5q) MDS patients achieving hematological response upon lenalidomide treatment, the drug reverts several transcriptional alterations in both del(5q) and non-del(5q) cells, but other lesions remain, which may be responsible for potential future relapses. Moreover, lack of hematological response is associated with the inability of lenalidomide to reverse transcriptional alterations. Collectively, this study reveals transcriptional alterations that could contribute to the pathogenesis and treatment response of del(5q) MDS.Nature ResearchDadun. Depósito Académico Digital Universidad de Navarra20242024-01-0120242024-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/113241reponame: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:10171/1132412026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
Single-cell transcriptional profile of CD34+ hematopoietic progenitor cells from del(5q) myelodysplastic syndromes and impact of lenalidomide |
| title |
Single-cell transcriptional profile of CD34+ hematopoietic progenitor cells from del(5q) myelodysplastic syndromes and impact of lenalidomide |
| spellingShingle |
Single-cell transcriptional profile of CD34+ hematopoietic progenitor cells from del(5q) myelodysplastic syndromes and impact of lenalidomide Serrano-Sanz, G. (Guillermo)|||/items/5ed5047b-1ad7-44a2-8674-de750c97b7c5 |
| title_short |
Single-cell transcriptional profile of CD34+ hematopoietic progenitor cells from del(5q) myelodysplastic syndromes and impact of lenalidomide |
| title_full |
Single-cell transcriptional profile of CD34+ hematopoietic progenitor cells from del(5q) myelodysplastic syndromes and impact of lenalidomide |
| title_fullStr |
Single-cell transcriptional profile of CD34+ hematopoietic progenitor cells from del(5q) myelodysplastic syndromes and impact of lenalidomide |
| title_full_unstemmed |
Single-cell transcriptional profile of CD34+ hematopoietic progenitor cells from del(5q) myelodysplastic syndromes and impact of lenalidomide |
| title_sort |
Single-cell transcriptional profile of CD34+ hematopoietic progenitor cells from del(5q) myelodysplastic syndromes and impact of lenalidomide |
| dc.creator.none.fl_str_mv |
Serrano-Sanz, G. (Guillermo)|||/items/5ed5047b-1ad7-44a2-8674-de750c97b7c5 Berastegui-Zufiaurre, N. (Nerea)|||/items/a609b1d4-fbed-4852-96eb-90e1cfe04e52 Díaz-Mazkiaran, A. (Aintzane)|||/items/8f723f6e-3569-43c9-ae70-07499bc3cac8 García-Olloqui, P. (Paula)|||/items/33aebcca-bf96-4a81-a74d-9fcd60b275cc Rodriguez-Res, C. (Carmen)|||/items/99683585-e42d-4e7b-8031-93320beed7fd Huerga-Dominguez, S. (Sofia)|||/items/a62c6e59-be71-4b34-b0b6-6deb286bbf3f Ainciburu-Fernández, M. (Marina)|||/items/71018cd2-9706-4dd0-84a9-77a8d03fef99 Vilas-Zornoza, A. (Amaia)|||/items/7435672d-e471-4409-8325-006fef27fb12 San-Martín-Uriz, P. (Patxi)|||/items/621b7a74-311b-4ff1-b688-53d810e30429 Aguirre-Ruiz, P. (Paula)|||/items/fd10df63-1585-43c5-bb82-d4357a15e7d8 Ullate-Agote, A. (Asier)|||/items/af0561e9-aebe-4e94-9cb1-6bb3aa8bf975 Ariceta, B. (Beñat)|||/items/e0060bfb-843a-4b76-a474-b79c0eeec803 Lamo-de-Espinosa-Vázquez-de-Sola, J.M. (José María)|||/items/75feb837-6d53-41fe-808d-4b70661db44e Acha, P. (Pamela)|||/items/7d12fe4a-6af1-41ff-8d28-87598f6ca8cb Calvete, O. (Oriol)|||/items/a22ae40f-38fc-4588-ad08-a83629184206 Jimenez-Solas, T. (Tamara)|||/items/7a4dbe5e-7060-4c1d-b632-9dd5089fe072 Molero, A. (Antonieta)|||/items/ea2d4363-f7f8-4859-b4f8-bf034d96ed9e Montoro-Gómez, M.J. (Maria Julia)|||/items/9bd28e22-a47c-43ed-9001-e3e5c95aebec Diez-Campelo, M. (Maria)|||/items/80adaceb-3fc4-44c2-bba0-2c88e6400317 Valcarcel, D. (David)|||/items/672eb58a-39da-45ab-85d2-58b2496cd1ab Sole, F. (Francisco)|||/items/cb283076-40b1-4363-81ee-5275088886bf Alfonso-Piérola, A. (Ana)|||/items/0212a5e6-923f-42aa-8ba3-b0ce4e1d6e10 Prosper-Cardoso, F. (Felipe)|||/items/3d1b0b82-06c3-4e63-8280-e903dc4dc0c1 Ezponda-Itoiz, T. (Teresa)|||/items/6941e85c-0814-4cde-9237-84a06fbf1697 Hernaez-Arrazola, M. (Mikel)|||/items/954a4ee7-b04c-4dc5-9bfc-7a48332c7e5a Ochoa-Álvarez, I. (Idoia)|||/items/6326dacc-419f-4156-a9c3-9e79cfcc6a3c |
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Serrano-Sanz, G. (Guillermo)|||/items/5ed5047b-1ad7-44a2-8674-de750c97b7c5 |
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Serrano-Sanz, G. (Guillermo)|||/items/5ed5047b-1ad7-44a2-8674-de750c97b7c5 Berastegui-Zufiaurre, N. (Nerea)|||/items/a609b1d4-fbed-4852-96eb-90e1cfe04e52 Díaz-Mazkiaran, A. (Aintzane)|||/items/8f723f6e-3569-43c9-ae70-07499bc3cac8 García-Olloqui, P. (Paula)|||/items/33aebcca-bf96-4a81-a74d-9fcd60b275cc Rodriguez-Res, C. (Carmen)|||/items/99683585-e42d-4e7b-8031-93320beed7fd Huerga-Dominguez, S. (Sofia)|||/items/a62c6e59-be71-4b34-b0b6-6deb286bbf3f Ainciburu-Fernández, M. (Marina)|||/items/71018cd2-9706-4dd0-84a9-77a8d03fef99 Vilas-Zornoza, A. (Amaia)|||/items/7435672d-e471-4409-8325-006fef27fb12 San-Martín-Uriz, P. (Patxi)|||/items/621b7a74-311b-4ff1-b688-53d810e30429 Aguirre-Ruiz, P. (Paula)|||/items/fd10df63-1585-43c5-bb82-d4357a15e7d8 Ullate-Agote, A. (Asier)|||/items/af0561e9-aebe-4e94-9cb1-6bb3aa8bf975 Ariceta, B. (Beñat)|||/items/e0060bfb-843a-4b76-a474-b79c0eeec803 Lamo-de-Espinosa-Vázquez-de-Sola, J.M. (José María)|||/items/75feb837-6d53-41fe-808d-4b70661db44e Acha, P. (Pamela)|||/items/7d12fe4a-6af1-41ff-8d28-87598f6ca8cb Calvete, O. (Oriol)|||/items/a22ae40f-38fc-4588-ad08-a83629184206 Jimenez-Solas, T. (Tamara)|||/items/7a4dbe5e-7060-4c1d-b632-9dd5089fe072 Molero, A. (Antonieta)|||/items/ea2d4363-f7f8-4859-b4f8-bf034d96ed9e Montoro-Gómez, M.J. (Maria Julia)|||/items/9bd28e22-a47c-43ed-9001-e3e5c95aebec Diez-Campelo, M. (Maria)|||/items/80adaceb-3fc4-44c2-bba0-2c88e6400317 Valcarcel, D. (David)|||/items/672eb58a-39da-45ab-85d2-58b2496cd1ab Sole, F. (Francisco)|||/items/cb283076-40b1-4363-81ee-5275088886bf Alfonso-Piérola, A. (Ana)|||/items/0212a5e6-923f-42aa-8ba3-b0ce4e1d6e10 Prosper-Cardoso, F. (Felipe)|||/items/3d1b0b82-06c3-4e63-8280-e903dc4dc0c1 Ezponda-Itoiz, T. (Teresa)|||/items/6941e85c-0814-4cde-9237-84a06fbf1697 Hernaez-Arrazola, M. (Mikel)|||/items/954a4ee7-b04c-4dc5-9bfc-7a48332c7e5a Ochoa-Álvarez, I. (Idoia)|||/items/6326dacc-419f-4156-a9c3-9e79cfcc6a3c |
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Berastegui-Zufiaurre, N. (Nerea)|||/items/a609b1d4-fbed-4852-96eb-90e1cfe04e52 Díaz-Mazkiaran, A. (Aintzane)|||/items/8f723f6e-3569-43c9-ae70-07499bc3cac8 García-Olloqui, P. (Paula)|||/items/33aebcca-bf96-4a81-a74d-9fcd60b275cc Rodriguez-Res, C. (Carmen)|||/items/99683585-e42d-4e7b-8031-93320beed7fd Huerga-Dominguez, S. (Sofia)|||/items/a62c6e59-be71-4b34-b0b6-6deb286bbf3f Ainciburu-Fernández, M. (Marina)|||/items/71018cd2-9706-4dd0-84a9-77a8d03fef99 Vilas-Zornoza, A. (Amaia)|||/items/7435672d-e471-4409-8325-006fef27fb12 San-Martín-Uriz, P. (Patxi)|||/items/621b7a74-311b-4ff1-b688-53d810e30429 Aguirre-Ruiz, P. (Paula)|||/items/fd10df63-1585-43c5-bb82-d4357a15e7d8 Ullate-Agote, A. (Asier)|||/items/af0561e9-aebe-4e94-9cb1-6bb3aa8bf975 Ariceta, B. (Beñat)|||/items/e0060bfb-843a-4b76-a474-b79c0eeec803 Lamo-de-Espinosa-Vázquez-de-Sola, J.M. (José María)|||/items/75feb837-6d53-41fe-808d-4b70661db44e Acha, P. (Pamela)|||/items/7d12fe4a-6af1-41ff-8d28-87598f6ca8cb Calvete, O. (Oriol)|||/items/a22ae40f-38fc-4588-ad08-a83629184206 Jimenez-Solas, T. (Tamara)|||/items/7a4dbe5e-7060-4c1d-b632-9dd5089fe072 Molero, A. (Antonieta)|||/items/ea2d4363-f7f8-4859-b4f8-bf034d96ed9e Montoro-Gómez, M.J. (Maria Julia)|||/items/9bd28e22-a47c-43ed-9001-e3e5c95aebec Diez-Campelo, M. (Maria)|||/items/80adaceb-3fc4-44c2-bba0-2c88e6400317 Valcarcel, D. (David)|||/items/672eb58a-39da-45ab-85d2-58b2496cd1ab Sole, F. (Francisco)|||/items/cb283076-40b1-4363-81ee-5275088886bf Alfonso-Piérola, A. (Ana)|||/items/0212a5e6-923f-42aa-8ba3-b0ce4e1d6e10 Prosper-Cardoso, F. (Felipe)|||/items/3d1b0b82-06c3-4e63-8280-e903dc4dc0c1 Ezponda-Itoiz, T. (Teresa)|||/items/6941e85c-0814-4cde-9237-84a06fbf1697 Hernaez-Arrazola, M. (Mikel)|||/items/954a4ee7-b04c-4dc5-9bfc-7a48332c7e5a Ochoa-Álvarez, I. (Idoia)|||/items/6326dacc-419f-4156-a9c3-9e79cfcc6a3c |
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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 |
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Dadun. Depósito Académico Digital Universidad de Navarra |
| description |
While myelodysplastic syndromes with del(5q) (del(5q) MDS) comprises a well-defined hematological subgroup, the molecular basis underlying its origin remains unknown. Using single cell RNA-seq (scRNA-seq) on CD34+ progenitors from del(5q) MDS patients, we have identified cells harboring the deletion, characterizing the transcriptional impact of this genetic insult on disease pathogenesis and treatment response. Interestingly, both del(5q) and non-del(5q) cells present similar transcriptional lesions, indicating that all cells, and not only those harboring the deletion, may contribute to aberrant hematopoietic differentiation. However, gene regulatory network (GRN) analyses reveal a group of regulons showing aberrant activity that could trigger altered hematopoiesis exclusively in del(5q) cells, pointing to a more prominent role of these cells in disease phenotype. In del(5q) MDS patients achieving hematological response upon lenalidomide treatment, the drug reverts several transcriptional alterations in both del(5q) and non-del(5q) cells, but other lesions remain, which may be responsible for potential future relapses. Moreover, lack of hematological response is associated with the inability of lenalidomide to reverse transcriptional alterations. Collectively, this study reveals transcriptional alterations that could contribute to the pathogenesis and treatment response of del(5q) MDS. |
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2024 |
| dc.date.none.fl_str_mv |
2024 2024-01-01 2024 2024-01-01 |
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journal article http://purl.org/coar/resource_type/c_6501 |
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info:eu-repo/semantics/article |
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article |
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https://hdl.handle.net/10171/113241 |
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https://hdl.handle.net/10171/113241 |
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Inglés eng |
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Inglés |
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eng |
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open access http://purl.org/coar/access_right/c_abf2 |
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open access http://purl.org/coar/access_right/c_abf2 |
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openAccess |
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application/pdf |
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Nature Research |
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Nature Research |
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reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
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