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| Status |
Public on May 07, 2008 |
| Title |
Differentially regulated genes in LT-HSC from control or Pbx1-null mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Self-renewal is a defining characteristic of stem cells, however the molecular pathways underlying its regulation are poorly understood. Here we demonstrate that conditional inactivation of the Pbx1 proto-oncogene in the hematopoietic compartment results in a progressive loss of long-term hematopoietic stem cells (LT-HSCs) that is associated with concomitant reduction in their quiescence, leading to a defect in the maintenance of self-renewal as assessed by serial transplantation. Transcriptional profiling revealed that multiple stem cell maintenance factors are perturbed in Pbx1-deficient LT-HSCs, which prematurely express a large subset of genes, including cell cycle regulators, normally expressed in non-self-renewing multipotent progenitors. A significant proportion of Pbx1-dependent genes are associated with the Tgf-b pathway, which serves a major role in maintaining HSC quiescence. Pbx1-deficient LT-HSCs are unable to up-regulate the cyclin dependent kinase inhibitor p57 in response to Tgf-b, providing a mechanism through which Pbx1 maintenance of stem cell self-renewal is achieved.
Keywords: genetic modification
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| Overall design |
Highly efficient Pbx1 deletion was induced with poly(I:C) in 3 young MxCre+.Pbx1f/f mutant or 2 MxCre-.Pbx1f/f control mice. LT-HSC (Lin-cKit+Sca1+CD34-CD135-) cells were prospectively sorted from bone marrow of individual mice harvested 4 weeks after the last injection of poly(I:C).
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| Contributor(s) |
Ficara F, Murphy MJ, Lin M, Cleary ML |
| Citation(s) |
18462698 |
| Submission date |
Sep 27, 2007 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Francesca Ficara |
| E-mail(s) |
francesca.ficara@humanitasresearch.it
|
| Organization name |
CNR/Istituto Clinico Humanitas
|
| Street address |
via Manzoni 56
|
| City |
Rozzano |
| State/province |
MI |
| ZIP/Postal code |
20089 |
| Country |
Italy |
| |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (5)
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| This SubSeries is part of SuperSeries: |
| GSE9198 |
Long-term hematopoietic stem cells and the proto-oncogene Pbx1 |
|
| Relations |
| BioProject |
PRJNA105243 |
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