|
| Status |
Public on Nov 29, 2012 |
| Title |
Expression data from RUNX1(41-214)-expressing and Runx1-knockout mice KSL cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Mutations of RUNX1 are detected in patients with myelodysplastic syndrome (MDS). In particular, C-terminal truncation mutations lack a transcription regulatory domain and have increased DNA binding through the runt homology domain (RHD). The expression of the RHD, RUNX1(41-214), in mouse hematopoietic cells induced progression to MDS and acute myeloid leukemia (AML). Analysis of pre-myelodysplastic animals revealed expansion of c-Kit+Sca-1+Lin- (KSL) cells and skewed differentiation to myeloid at the expense of the lymphoid lineage. These abnormalities correlate with the phenotype of Runx1-deficient animals, as expected given the reported dominant-negative role of C-terminal mutations over the full-length RUNX1. However, MDS is not observed in Runx1-deficient animals. Gene expression profiling revealed that RUNX1(41-214) KSLs have an overlapping yet distinct gene expression profile from Runx1-deficient animals. Moreover, an unexpected parallel was observed between the hematopoietic phenotype of RUNX1(41-214) and aged animals. Genes deregulated in RUNX1(41-214), but not in Runx1-deficient animals, were inversely correlated with the aging gene signature of hematopoietic stem cells (HSC), suggesting that disruption of the expression of genes related to normal aging by RUNX1 mutations contributes to development of MDS. The data presented here provide insights into the mechanisms of development of MDS in HSCs by C-terminal mutations of RUNX1.
|
| |
|
| Overall design |
Gene expression analysis were performed on c-Kit+/Sca-1+/Lin-/IL7Ra- (KSL) cells sorted from RUNX1(41-214)-expressing and Runx1-knockout (Runx1floxed/floxed MxCre+/-) and control mice (Runx1floxed/floxedMxCre-/-).
|
| |
|
| Contributor(s) |
Matsuura S, Stevenson KE, Neuberg DS, Zhang D |
| Citation(s) |
22919028 |
| Submission date |
Aug 15, 2012 |
| Last update date |
May 04, 2018 |
| Contact name |
Dong-Er Zhang |
| E-mail(s) |
d7zhang@ucsd.edu
|
| Phone |
(858)822-5372
|
| Fax |
(858)822-5433
|
| URL |
http://www.biology.ucsd.edu/labs/zhang/
|
| Organization name |
University of California San Diego
|
| Department |
Moores UCSD Cancer Center
|
| Lab |
Dong-Er Zhang
|
| Street address |
3855 Health Sciences Drive
|
| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92093 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL8321 |
[Mouse430A_2] Affymetrix Mouse Genome 430A 2.0 Array |
|
| Samples (9)
|
|
| Relations |
| BioProject |
PRJNA172941 |
Less...
More...