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A Senescence-Like Cell-Cycle Arrest Occurs During Megakaryocytic Maturation: Implications for Physiological and Pathological Megakaryocytic Proliferation
Thrombopoietin (TPO) via signaling through its cognate receptor MPL is a key cytokine involved in the regulation of megakaryocyte differentiation leading to platelet production. Mature megakaryocytes are polyploid cells that have arrested DNA replication and cellular proliferation but continue susta...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935456/ https://www.ncbi.nlm.nih.gov/pubmed/20838657 http://dx.doi.org/10.1371/journal.pbio.1000476 |
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author | Besancenot, Rodolphe Chaligné, Ronan Tonetti, Carole Pasquier, Florence Marty, Caroline Lécluse, Yann Vainchenker, William Constantinescu, Stefan N. Giraudier, Stéphane |
author_facet | Besancenot, Rodolphe Chaligné, Ronan Tonetti, Carole Pasquier, Florence Marty, Caroline Lécluse, Yann Vainchenker, William Constantinescu, Stefan N. Giraudier, Stéphane |
author_sort | Besancenot, Rodolphe |
collection | PubMed |
description | Thrombopoietin (TPO) via signaling through its cognate receptor MPL is a key cytokine involved in the regulation of megakaryocyte differentiation leading to platelet production. Mature megakaryocytes are polyploid cells that have arrested DNA replication and cellular proliferation but continue sustained protein synthesis. Here, we show that TPO induces cell-cycle arrest in the megakaryocytic UT7-MPL cell line by the activation of the ERK/MAPK pathway, induction of p21CIP transcription, and senescence markers through EGR1 activation. A similar senescence-like process was also detected in normal primary postmitotic megakaryocytes. In contrast, senescence was not observed in malignant megakaryocytes derived from primary myelofibrosis patients (a form of chronic myeloid hemopathy). Our data indicate that polyploid mature megakaryocytes receive signals from TPO to arrest cell proliferation and enter a senescent-like state. An escape from this physiological process may be associated with certain myeloproliferative neoplasms leading to abnormal megakaryocytic proliferation. |
format | Text |
id | pubmed-2935456 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-29354562010-09-13 A Senescence-Like Cell-Cycle Arrest Occurs During Megakaryocytic Maturation: Implications for Physiological and Pathological Megakaryocytic Proliferation Besancenot, Rodolphe Chaligné, Ronan Tonetti, Carole Pasquier, Florence Marty, Caroline Lécluse, Yann Vainchenker, William Constantinescu, Stefan N. Giraudier, Stéphane PLoS Biol Research Article Thrombopoietin (TPO) via signaling through its cognate receptor MPL is a key cytokine involved in the regulation of megakaryocyte differentiation leading to platelet production. Mature megakaryocytes are polyploid cells that have arrested DNA replication and cellular proliferation but continue sustained protein synthesis. Here, we show that TPO induces cell-cycle arrest in the megakaryocytic UT7-MPL cell line by the activation of the ERK/MAPK pathway, induction of p21CIP transcription, and senescence markers through EGR1 activation. A similar senescence-like process was also detected in normal primary postmitotic megakaryocytes. In contrast, senescence was not observed in malignant megakaryocytes derived from primary myelofibrosis patients (a form of chronic myeloid hemopathy). Our data indicate that polyploid mature megakaryocytes receive signals from TPO to arrest cell proliferation and enter a senescent-like state. An escape from this physiological process may be associated with certain myeloproliferative neoplasms leading to abnormal megakaryocytic proliferation. Public Library of Science 2010-09-07 /pmc/articles/PMC2935456/ /pubmed/20838657 http://dx.doi.org/10.1371/journal.pbio.1000476 Text en Besancenot et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Besancenot, Rodolphe Chaligné, Ronan Tonetti, Carole Pasquier, Florence Marty, Caroline Lécluse, Yann Vainchenker, William Constantinescu, Stefan N. Giraudier, Stéphane A Senescence-Like Cell-Cycle Arrest Occurs During Megakaryocytic Maturation: Implications for Physiological and Pathological Megakaryocytic Proliferation |
title | A Senescence-Like Cell-Cycle Arrest Occurs During Megakaryocytic Maturation: Implications for Physiological and Pathological Megakaryocytic Proliferation |
title_full | A Senescence-Like Cell-Cycle Arrest Occurs During Megakaryocytic Maturation: Implications for Physiological and Pathological Megakaryocytic Proliferation |
title_fullStr | A Senescence-Like Cell-Cycle Arrest Occurs During Megakaryocytic Maturation: Implications for Physiological and Pathological Megakaryocytic Proliferation |
title_full_unstemmed | A Senescence-Like Cell-Cycle Arrest Occurs During Megakaryocytic Maturation: Implications for Physiological and Pathological Megakaryocytic Proliferation |
title_short | A Senescence-Like Cell-Cycle Arrest Occurs During Megakaryocytic Maturation: Implications for Physiological and Pathological Megakaryocytic Proliferation |
title_sort | senescence-like cell-cycle arrest occurs during megakaryocytic maturation: implications for physiological and pathological megakaryocytic proliferation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935456/ https://www.ncbi.nlm.nih.gov/pubmed/20838657 http://dx.doi.org/10.1371/journal.pbio.1000476 |
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