The Microtubule Plus-End Tracking Protein CLASP2 Is Required for Hematopoiesis and Hematopoietic Stem Cell Maintenance
Mammalian CLASPs are microtubule plus-end tracking proteins whose essential function as regulators of microtubule behavior has been studied mainly in cultured cells. We show here that absence of murine CLASP2 in vivo results in thrombocytopenia, progressive anemia, and pancytopenia, due to defects i...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2012-10-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124712002811 |
| _version_ | 1819026950182666240 |
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| author | Ksenija Drabek Laura Gutiérrez Marcel Vermeij Thomas Clapes Sunita R. Patel Jean-Charles Boisset Jeffrey van Haren Ana L. Pereira Zhe Liu Umut Akinci Tatjana Nikolic Wilfred van IJcken Mirjam van den Hout Marjolein Meinders Clara Melo Clara Sambade Dubravka Drabek Rudi W. Hendriks Sjaak Philipsen Mieke Mommaas Frank Grosveld Helder Maiato Joseph E. Italiano, Jr. Catherine Robin Niels Galjart |
| author_facet | Ksenija Drabek Laura Gutiérrez Marcel Vermeij Thomas Clapes Sunita R. Patel Jean-Charles Boisset Jeffrey van Haren Ana L. Pereira Zhe Liu Umut Akinci Tatjana Nikolic Wilfred van IJcken Mirjam van den Hout Marjolein Meinders Clara Melo Clara Sambade Dubravka Drabek Rudi W. Hendriks Sjaak Philipsen Mieke Mommaas Frank Grosveld Helder Maiato Joseph E. Italiano, Jr. Catherine Robin Niels Galjart |
| author_sort | Ksenija Drabek |
| collection | DOAJ |
| description | Mammalian CLASPs are microtubule plus-end tracking proteins whose essential function as regulators of microtubule behavior has been studied mainly in cultured cells. We show here that absence of murine CLASP2 in vivo results in thrombocytopenia, progressive anemia, and pancytopenia, due to defects in megakaryopoiesis, in erythropoiesis, and in the maintenance of hematopoietic stem cell activity. Furthermore, microtubule stability and organization are affected upon attachment of Clasp2 knockout hematopoietic stem-cell-enriched populations, and these cells do not home efficiently toward their bone marrow niche. Strikingly, CLASP2-deficient hematopoietic stem cells contain severely reduced mRNA levels of c-Mpl, which encodes the thrombopoietin receptor, an essential factor for megakaryopoiesis and hematopoietic stem cell maintenance. Our data suggest that thrombopoietin signaling is impaired in Clasp2 knockout mice. We propose that the CLASP2-mediated stabilization of microtubules is required for proper attachment, homing, and maintenance of hematopoietic stem cells and that this is necessary to sustain c-Mpl transcription. |
| first_indexed | 2024-12-21T05:34:43Z |
| format | Article |
| id | doaj.art-3e5cff7148ce447398adad76a986d785 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-21T05:34:43Z |
| publishDate | 2012-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-3e5cff7148ce447398adad76a986d7852022-12-21T19:14:27ZengElsevierCell Reports2211-12472012-10-012478178810.1016/j.celrep.2012.08.040The Microtubule Plus-End Tracking Protein CLASP2 Is Required for Hematopoiesis and Hematopoietic Stem Cell MaintenanceKsenija Drabek0Laura Gutiérrez1Marcel Vermeij2Thomas Clapes3Sunita R. Patel4Jean-Charles Boisset5Jeffrey van Haren6Ana L. Pereira7Zhe Liu8Umut Akinci9Tatjana Nikolic10Wilfred van IJcken11Mirjam van den Hout12Marjolein Meinders13Clara Melo14Clara Sambade15Dubravka Drabek16Rudi W. Hendriks17Sjaak Philipsen18Mieke Mommaas19Frank Grosveld20Helder Maiato21Joseph E. Italiano, Jr.22Catherine Robin23Niels Galjart24Department of Cell Biology and Genetics, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Cell Biology and Genetics, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Pathology, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Cell Biology and Genetics, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsHematology Division, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USADepartment of Cell Biology and Genetics, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Cell Biology and Genetics, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Cell Biology and Genetics, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Cell Biology and Genetics, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Cell Biology and Genetics, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Pulmonary Medicine, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsErasmus Center for Biomics, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsErasmus Center for Biomics, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Plesmanlaan 125, 1066 CX Amsterdam, The NetherlandsChromosome Instability & Dynamics Laboratory-Instituto de Biologia Molecular e Celular, Faculdade de Medicina, Universidade do Porto, 4200-465 Porto, PortugalCancer Biology, IPATIMUP, and Medical Faculty of Porto, Faculdade de Medicina, Universidade do Porto, 4200-465 Porto, PortugalDepartment of Cell Biology and Genetics, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Pulmonary Medicine, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Cell Biology and Genetics, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsCenter for Electron Microscopy, Department of Molecular Cell Biology, Leiden University Medical Center, 2300 RA Leiden, The NetherlandsDepartment of Cell Biology and Genetics, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsChromosome Instability & Dynamics Laboratory-Instituto de Biologia Molecular e Celular, Faculdade de Medicina, Universidade do Porto, 4200-465 Porto, PortugalHematology Division, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USADepartment of Cell Biology and Genetics, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Cell Biology and Genetics, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsMammalian CLASPs are microtubule plus-end tracking proteins whose essential function as regulators of microtubule behavior has been studied mainly in cultured cells. We show here that absence of murine CLASP2 in vivo results in thrombocytopenia, progressive anemia, and pancytopenia, due to defects in megakaryopoiesis, in erythropoiesis, and in the maintenance of hematopoietic stem cell activity. Furthermore, microtubule stability and organization are affected upon attachment of Clasp2 knockout hematopoietic stem-cell-enriched populations, and these cells do not home efficiently toward their bone marrow niche. Strikingly, CLASP2-deficient hematopoietic stem cells contain severely reduced mRNA levels of c-Mpl, which encodes the thrombopoietin receptor, an essential factor for megakaryopoiesis and hematopoietic stem cell maintenance. Our data suggest that thrombopoietin signaling is impaired in Clasp2 knockout mice. We propose that the CLASP2-mediated stabilization of microtubules is required for proper attachment, homing, and maintenance of hematopoietic stem cells and that this is necessary to sustain c-Mpl transcription.http://www.sciencedirect.com/science/article/pii/S2211124712002811 |
| spellingShingle | Ksenija Drabek Laura Gutiérrez Marcel Vermeij Thomas Clapes Sunita R. Patel Jean-Charles Boisset Jeffrey van Haren Ana L. Pereira Zhe Liu Umut Akinci Tatjana Nikolic Wilfred van IJcken Mirjam van den Hout Marjolein Meinders Clara Melo Clara Sambade Dubravka Drabek Rudi W. Hendriks Sjaak Philipsen Mieke Mommaas Frank Grosveld Helder Maiato Joseph E. Italiano, Jr. Catherine Robin Niels Galjart The Microtubule Plus-End Tracking Protein CLASP2 Is Required for Hematopoiesis and Hematopoietic Stem Cell Maintenance Cell Reports |
| title | The Microtubule Plus-End Tracking Protein CLASP2 Is Required for Hematopoiesis and Hematopoietic Stem Cell Maintenance |
| title_full | The Microtubule Plus-End Tracking Protein CLASP2 Is Required for Hematopoiesis and Hematopoietic Stem Cell Maintenance |
| title_fullStr | The Microtubule Plus-End Tracking Protein CLASP2 Is Required for Hematopoiesis and Hematopoietic Stem Cell Maintenance |
| title_full_unstemmed | The Microtubule Plus-End Tracking Protein CLASP2 Is Required for Hematopoiesis and Hematopoietic Stem Cell Maintenance |
| title_short | The Microtubule Plus-End Tracking Protein CLASP2 Is Required for Hematopoiesis and Hematopoietic Stem Cell Maintenance |
| title_sort | microtubule plus end tracking protein clasp2 is required for hematopoiesis and hematopoietic stem cell maintenance |
| url | http://www.sciencedirect.com/science/article/pii/S2211124712002811 |
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