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Series GSE9188 Query DataSets for GSE9188
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
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
 
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).
 
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
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (5)
GSM232046 LT-HSC_Control_Rep1
GSM232047 LT-HSC_Control_Rep2
GSM232048 LT-HSC_Mutant_Rep1
This SubSeries is part of SuperSeries:
GSE9198 Long-term hematopoietic stem cells and the proto-oncogene Pbx1
Relations
BioProject PRJNA105243

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE9188_RAW.tar 17.6 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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