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| Status |
Public on Jul 06, 2013 |
| Title |
SCL and c-Kit controlled gene expression in erythroid progenitor cell line |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
SCL/TAL1, a tissue-specific transcription factor of the basic helix-loop-helix (bHLH) family, and c-Kit, a tyrosine kinase receptor, control hematopoietic stem cell survival and quiescence. Here we report that SCL and c-Kit signaling control a common gene expression signature, of which 19 genes are associated with apoptosis. In vivo, SCL levels are limiting for the clonal expansion of Kit+ multipotent and erythroid progenitors. In addition, increased SCL expression specifically enhances the sensitivity of multipotent and megakaryocyte/erythroid progenitors to Steel factor (KIT ligand), whilst a DNA binding mutant antagonizes KIT function and induces apoptosis in progenitors. We conclude that Scl operates downstream of Kit to support the survival of megakaryocyte/erythroid progenitors. Finally, higher SCL expression upregulates Kit in normal bone marrow cells and increases chimerism after bone marrow transplantation, indicating that Scl is also upstream of Kit. We conclude that Scl and Kit establish a positive feedback loop in multipotent and megakaryocyte/erythroid progenitors.
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| Overall design |
c-Kit regulated genes were extrapolated from gene expression profiles of TF-1 erythroid progenitor cells (empty MSCV vector) stimulated with SF (Kit ligand), Epo or GM-CSF. Second, SCL-regulated genes were obtained by expressing a DNA binding-defective SCL mutant (DbSCL) and selecting genes that were differentially expressed in bSCL cells versus control cells (MSCV) stimulated with the same cytokines.
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| Contributor(s) |
Tremblay M, Lacombe J, Lemieux S, Hoang T |
| Citation(s) |
23836559 |
| |
| Submission date |
Jul 05, 2013 |
| Last update date |
Aug 10, 2018 |
| Contact name |
mathieu tremblay |
| E-mail(s) |
m.tremblay@umontreal.ca
|
| Organization name |
Université de Montréal/IRIC
|
| Street address |
2950 Chemin de Polytechnique, pav marcelle-coutu 1432
|
| City |
Montreal |
| State/province |
QC |
| ZIP/Postal code |
h3t 1j4 |
| Country |
Canada |
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| Platforms (1) |
| GPL96 |
[HG-U133A] Affymetrix Human Genome U133A Array |
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| Samples (5)
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| Relations |
| BioProject |
PRJNA210621 |
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