Linked Life Data

21596846

Source:http://linkedlifedata.com/resource/pubmed/id/21596846

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-7-22
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
21
pubmed:volume
118
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
723-35
pubmed:meshHeading
pubmed-meshheading:21596846-Animals, pubmed-meshheading:21596846-Basic Helix-Loop-Helix Transcription Factors, pubmed-meshheading:21596846-Bone Marrow Cells, pubmed-meshheading:21596846-Cell Division, pubmed-meshheading:21596846-Cell Lineage, pubmed-meshheading:21596846-Cells, Cultured, pubmed-meshheading:21596846-Cyclin-Dependent Kinase Inhibitor p21, pubmed-meshheading:21596846-Cytoplasm, pubmed-meshheading:21596846-Gene Knockdown Techniques, pubmed-meshheading:21596846-Hematopoietic Stem Cells, pubmed-meshheading:21596846-Megakaryocytes, pubmed-meshheading:21596846-Mice, pubmed-meshheading:21596846-Microscopy, Electron, pubmed-meshheading:21596846-Polyploidy, pubmed-meshheading:21596846-Proto-Oncogene Proteins, pubmed-meshheading:21596846-Thrombocytopenia, pubmed-meshheading:21596846-Thrombopoiesis
pubmed:year
2011
pubmed:articleTitle
SCL-mediated regulation of the cell-cycle regulator p21 is critical for murine megakaryopoiesis.
pubmed:affiliation
Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't