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| Status |
Public on Jul 11, 2011 |
| Title |
Genome -wide identification of SCL's target genes in Megakaryocyte progenitors |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Megakaryopoiesis is a complex process that involves major cellular 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 SCL/TAL1 is required for specification of the megakaryocytic lineage from hematopoietic progenitors. Here, we report that it also critically controls terminal megakaryocyte maturation. In vivo depletion of SCL specifically in the megakaryocytic lineage affects all key attributes of megakaryocyte progenitors (MkPs), namely proliferation, ploidisation, cytoplasmic maturation, as well as platelet production. Genome-wide expression analysis reveals increased expression of the cell cycle regulator p21 in Scl-deleted MkPs. Importantly, P21 knockdown-mediated rescue assays in Scl-deleted MkPs show full restoration of cell cycle progression and partial rescue of the nuclear and cytoplasmic maturation defects. Therefore, SCL-mediated transcriptional control of p21 is critical for maturation of MkPs. Our study provides a mechanistic link between one of the major hematopoietic transcriptional regulators, cell cycle progression and megakaryocytic differentiation.
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| Overall design |
Total RNA extracted from control TGPF4-CRE;SCL wt/wt sorted MK progenitors was compared to total RNA extracted from TGPF4-CRE;SCL fl/fl MK progenitors cells where Scl was completely excised
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| Contributor(s) |
Chagraoui H, Soneji S, Porcher C |
| Citation(s) |
21596846 |
| Submission date |
Oct 27, 2010 |
| Last update date |
Jan 18, 2013 |
| Contact name |
Hedia Chagraoui |
| E-mail(s) |
hedia.chagraoui@imm.ox.ac.uk
|
| Phone |
00441865222309
|
| Organization name |
Weatherall Institute of Molecular Medicine
|
| Department |
Molecular Hematology Unit
|
| Lab |
PORCHER/VYAS lab
|
| Street address |
john radcliffe hospital headley way headington
|
| City |
Oxford |
| ZIP/Postal code |
OX3 9DS |
| Country |
United Kingdom |
| |
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| Platforms (1) |
| GPL6105 |
Illumina mouse-6 v1.1 expression beadchip |
|
| Samples (6)
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| Relations |
| BioProject |
PRJNA131897 |
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