Project description:The transcriptome of LT-HSC (CD34+CD38-CD45RA+CD90+CD49f+) and ST-HSC (CD34+CD38-CD45RA+CD90-CD49f-) from healthy adult human Bone Marrow Cells were assessed by RNA-seq.
Project description:We have developed a new conditional transgenic mouse showing that MLL-ENL, at an endogenous-like expression level, induces leukemic transformation selectively in LT-HSCs. To investigate the molecular mechanism of leukemic transformation in LT-HSCs conditionally expressing MLL-ENL, we preliminarily performed comprehensive gene expression profiling of CreER-transduced LT-HSCs and ST-HSCs using cDNA microarray analysis. For initial screening of candidate genes invloved in the leukemic transformation, total RNA was extracted from colony-forming cells derived from LT-HSCs and ST-HSCs transduced with CreER or mock. Four samples were analyzed, and CreER-transduced LT/ST-HSC-derived cells were compared with mock-transduced LT/ST-HSC-derived cells, while CreER/mock-transduced LT-HSC-derived cells were compared with CreER/mock-transduced ST-HSC-derived cells.
Project description:We have developed a new conditional transgenic mouse showing that MLL-ENL, at an endogenous-like expression level, induces leukemic transformation selectively in LT-HSCs. To investigate the molecular mechanism of leukemic transformation in LT-HSCs conditionally expressing MLL-ENL, we preliminarily performed comprehensive gene expression profiling of CreER-transduced LT-HSCs and ST-HSCs using cDNA microarray analysis.
Project description:Total body irradiation (TBI) of mice using two dose rates, conventional dose rate (CDR) versus flash dose rate (FLASH), induced transient decrease of number of LT-HScs in bone marrow and a total recovery of these cells 15 days after TBI We used microarrays to detail the global programme of gene expression underlying the recovery of LT-HSCs and identified distinct classes of up or down- regulated genes according the modality of irradiation
Project description: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. Experiment Overall Design: LT-HSC (Lin-cKit+Sca1+CD34-CD135-) and ST-HSC (Lin-cKit+Sca1+CD34+CD135-) cells were prospectively sorted from the BM of MxCre-.Pbx1f/f control mice harvested 4 weeks after the last injection of poly(I:C).
Project description:We isolated murine fetal liver and murine adult bone marrow and FACS sorted LT-HSCs, ST-HSCs and MPPs. We used global expression analysis by microarray to compare regulated genesets in different HSC populations in fetal and adult.
Project description:The vulnerability of bone marrow hematopoiesis to perturbations of cholesterol metabolism is well documented, while the underlying cellular and molecular mechanisms remain poorly understood. Here we reveal a distinct cholesterol metabolic signature of hematopoietic stem cells (HSCs) within the hematopoietic compartment.To identify the phenotype switching and function variation in BM LT-HSCs with HCD treatment, we performed RNA-seq of LT-HSCs from the bone marrow of mice with or without3-month HCD treatment.