ArrayExpress Uploader07941arrayexpress_sid6Self-renewal is a defining characteristic of stem cells, however the molecular pathways underlying its regulation are poorly understood....18462698E-GEOD-9188/profile/8773/arrayexpressuploader05bonebone marrowcellcompartmentstem cellDec.12, 2014Falsetranscription-profiling-of-mouse-long-term-hsc-froE-GEOD-9188_A-AFFY-45Transcription profiling of mouse long term HSC from control or Pbx1-null miceNov.18, 2014Self-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. Experiment 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).http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-9188mousehttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-9188/samples/