p19INK4d Controls Hematopoietic Stem Cells in a Cell-Autonomous Manner during Genotoxic Stress and through the Microenvironment during Aging
Hematopoietic stem cells (HSCs) are characterized by the capacity for self-renewal and the ability to reconstitute the entire hematopoietic compartment. Thrombopoietin maintains adult HSCs in a quiescent state through the induction of cell cycle inhibitors p57Kip2 and p19INK4d. Using the p19INK4d−/−...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-12-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671114003270 |
| _version_ | 1819127490014085120 |
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| author | Morgane Hilpert Céline Legrand Dominique Bluteau Natalie Balayn Aline Betems Olivier Bluteau Jean-Luc Villeval Fawzia Louache Patrick Gonin Najet Debili Isabelle Plo William Vainchenker Laure Gilles Hana Raslova |
| author_facet | Morgane Hilpert Céline Legrand Dominique Bluteau Natalie Balayn Aline Betems Olivier Bluteau Jean-Luc Villeval Fawzia Louache Patrick Gonin Najet Debili Isabelle Plo William Vainchenker Laure Gilles Hana Raslova |
| author_sort | Morgane Hilpert |
| collection | DOAJ |
| description | Hematopoietic stem cells (HSCs) are characterized by the capacity for self-renewal and the ability to reconstitute the entire hematopoietic compartment. Thrombopoietin maintains adult HSCs in a quiescent state through the induction of cell cycle inhibitors p57Kip2 and p19INK4d. Using the p19INK4d−/− mouse model, we investigated the role of p19INK4d in basal and stress-induced hematopoiesis. We demonstrate that p19INK4d is involved in the regulation of HSC quiescence by inhibition of the G0/G1 cell cycle transition. Under genotoxic stress conditions, the absence of p19INK4d in HSCs leads to accelerated cell cycle exit, accumulation of DNA double-strand breaks, and apoptosis when cells progress to the S/G2-M stages of the cell cycle. Moreover, p19INK4d controls the HSC microenvironment through negative regulation of megakaryopoiesis. Deletion of p19INK4d results in megakaryocyte hyperproliferation and increased transforming growth factor β1 secretion. This leads to fibrosis in the bone marrow and spleen, followed by loss of HSCs during aging. |
| first_indexed | 2024-12-22T08:12:45Z |
| format | Article |
| id | doaj.art-8d362dff690f402983d266a8c9926945 |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-22T08:12:45Z |
| publishDate | 2014-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-8d362dff690f402983d266a8c99269452022-12-21T18:32:59ZengElsevierStem Cell Reports2213-67112014-12-01361085110210.1016/j.stemcr.2014.10.005p19INK4d Controls Hematopoietic Stem Cells in a Cell-Autonomous Manner during Genotoxic Stress and through the Microenvironment during AgingMorgane Hilpert0Céline Legrand1Dominique Bluteau2Natalie Balayn3Aline Betems4Olivier Bluteau5Jean-Luc Villeval6Fawzia Louache7Patrick Gonin8Najet Debili9Isabelle Plo10William Vainchenker11Laure Gilles12Hana Raslova13Institut National de la Santé et de la Recherche Médicale, U1009, Equipe labellisée Ligue Nationale contre le Cancer, 114 rue Edouard Vaillant, 94805 Villejuif, FranceInstitut National de la Santé et de la Recherche Médicale, U1009, Equipe labellisée Ligue Nationale contre le Cancer, 114 rue Edouard Vaillant, 94805 Villejuif, FranceInstitut National de la Santé et de la Recherche Médicale, U1009, Equipe labellisée Ligue Nationale contre le Cancer, 114 rue Edouard Vaillant, 94805 Villejuif, FranceInstitut National de la Santé et de la Recherche Médicale, U1009, Equipe labellisée Ligue Nationale contre le Cancer, 114 rue Edouard Vaillant, 94805 Villejuif, FranceInstitut National de la Santé et de la Recherche Médicale, U1009, Equipe labellisée Ligue Nationale contre le Cancer, 114 rue Edouard Vaillant, 94805 Villejuif, FranceInstitut National de la Santé et de la Recherche Médicale, U1009, Equipe labellisée Ligue Nationale contre le Cancer, 114 rue Edouard Vaillant, 94805 Villejuif, FranceInstitut National de la Santé et de la Recherche Médicale, U1009, Equipe labellisée Ligue Nationale contre le Cancer, 114 rue Edouard Vaillant, 94805 Villejuif, FranceInstitut National de la Santé et de la Recherche Médicale, U1009, Equipe labellisée Ligue Nationale contre le Cancer, 114 rue Edouard Vaillant, 94805 Villejuif, FranceUniversity Paris Sud, 114, rue Edouard Vaillant, 94805 Villejuif, FranceInstitut National de la Santé et de la Recherche Médicale, U1009, Equipe labellisée Ligue Nationale contre le Cancer, 114 rue Edouard Vaillant, 94805 Villejuif, FranceInstitut National de la Santé et de la Recherche Médicale, U1009, Equipe labellisée Ligue Nationale contre le Cancer, 114 rue Edouard Vaillant, 94805 Villejuif, FranceInstitut National de la Santé et de la Recherche Médicale, U1009, Equipe labellisée Ligue Nationale contre le Cancer, 114 rue Edouard Vaillant, 94805 Villejuif, FranceInstitut National de la Santé et de la Recherche Médicale, U1009, Equipe labellisée Ligue Nationale contre le Cancer, 114 rue Edouard Vaillant, 94805 Villejuif, FranceInstitut National de la Santé et de la Recherche Médicale, U1009, Equipe labellisée Ligue Nationale contre le Cancer, 114 rue Edouard Vaillant, 94805 Villejuif, FranceHematopoietic stem cells (HSCs) are characterized by the capacity for self-renewal and the ability to reconstitute the entire hematopoietic compartment. Thrombopoietin maintains adult HSCs in a quiescent state through the induction of cell cycle inhibitors p57Kip2 and p19INK4d. Using the p19INK4d−/− mouse model, we investigated the role of p19INK4d in basal and stress-induced hematopoiesis. We demonstrate that p19INK4d is involved in the regulation of HSC quiescence by inhibition of the G0/G1 cell cycle transition. Under genotoxic stress conditions, the absence of p19INK4d in HSCs leads to accelerated cell cycle exit, accumulation of DNA double-strand breaks, and apoptosis when cells progress to the S/G2-M stages of the cell cycle. Moreover, p19INK4d controls the HSC microenvironment through negative regulation of megakaryopoiesis. Deletion of p19INK4d results in megakaryocyte hyperproliferation and increased transforming growth factor β1 secretion. This leads to fibrosis in the bone marrow and spleen, followed by loss of HSCs during aging.http://www.sciencedirect.com/science/article/pii/S2213671114003270 |
| spellingShingle | Morgane Hilpert Céline Legrand Dominique Bluteau Natalie Balayn Aline Betems Olivier Bluteau Jean-Luc Villeval Fawzia Louache Patrick Gonin Najet Debili Isabelle Plo William Vainchenker Laure Gilles Hana Raslova p19INK4d Controls Hematopoietic Stem Cells in a Cell-Autonomous Manner during Genotoxic Stress and through the Microenvironment during Aging Stem Cell Reports |
| title | p19INK4d Controls Hematopoietic Stem Cells in a Cell-Autonomous Manner during Genotoxic Stress and through the Microenvironment during Aging |
| title_full | p19INK4d Controls Hematopoietic Stem Cells in a Cell-Autonomous Manner during Genotoxic Stress and through the Microenvironment during Aging |
| title_fullStr | p19INK4d Controls Hematopoietic Stem Cells in a Cell-Autonomous Manner during Genotoxic Stress and through the Microenvironment during Aging |
| title_full_unstemmed | p19INK4d Controls Hematopoietic Stem Cells in a Cell-Autonomous Manner during Genotoxic Stress and through the Microenvironment during Aging |
| title_short | p19INK4d Controls Hematopoietic Stem Cells in a Cell-Autonomous Manner during Genotoxic Stress and through the Microenvironment during Aging |
| title_sort | p19ink4d controls hematopoietic stem cells in a cell autonomous manner during genotoxic stress and through the microenvironment during aging |
| url | http://www.sciencedirect.com/science/article/pii/S2213671114003270 |
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