SCL-mediated regulation of the cell-cycle regulator p21 is critical for murine megakaryopoiesis

Chagraoui, Hedia and Kassouf, Mira and Banerjee, Sreemoti and Goardon, Nicolas and Clark, Kevin and Atzberger, Ann and Pearce, Andrew C. and Skoda, Radek C. and Ferguson, David J. P. and Watson, Steve P. and Vyas, Paresh and Porcher, Catherine. (2011) SCL-mediated regulation of the cell-cycle regulator p21 is critical for murine megakaryopoiesis. Blood, Vol. 118, H. 3. pp. 723-735.

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Official URL: http://edoc.unibas.ch/dok/A6005121

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Megakaryopoiesis is a complex process that involves major cellular and nuclear changes and relies on controlled coordination of cellular proliferation and differentiation. These mechanisms are orchestrated in part by transcriptional regulators. The key hematopoietic transcription factor stem cell leukemia (SCL)/TAL1 is required in early hematopoietic progenitors for specification of the megakaryocytic lineage. These early functions have, so far, prevented full investigation of its role in megakaryocyte development in loss-of-function studies. Here, we report that SCL critically controls terminal megakaryocyte maturation. In vivo deletion of Scl specifically in the megakaryocytic lineage affects all key attributes of megakaryocyte progenitors (MkPs), namely, proliferation, ploidization, cytoplasmic maturation, and platelet release. Genome-wide expression analysis reveals increased expression of the cell-cycle regulator p21 in Scl-deleted MkPs. Importantly, p21 knockdown-mediated rescue of Scl-mutant MkPs shows full restoration of cell-cycle progression and partial rescue of the nuclear and cytoplasmic maturation defects. Therefore, SCL-mediated transcriptional control of p21 is essential for terminal maturation of MkPs. Our study provides a mechanistic link between a major hematopoietic transcriptional regulator, cell-cycle progression, and megakaryocytic differentiation.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Experimental Hematology (Skoda)
03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Hämatologie > Molekulare Medizin (Skoda)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Hämatologie > Molekulare Medizin (Skoda)
UniBasel Contributors:Skoda, Radek C.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Society of Hematology
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 May 2015 08:45
Deposited On:27 Feb 2014 15:45

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