Project description:To identify the genes, which led to the augmented hematopoiesis in DS-iPS cells, we performed gene expression profiling of D12-DS-iPS cells (DS-iPS-T32, DS-iPS-T33 and DS-iPS-T31) and control hiPS cells (253G1, 253G4 and A31) generated by 3 factors. In the comparison of gene expression levels in each DS-iPS cell clone with the average of these in control iPS cell clones, 972 genes showed more than 2-fold increased expression, and 1118 genes showed decreased expression in all DS-iPS cell clones. Among these upregulated genes, 61 genes including GATA1 were involved in hematopoiesis-related genes according to Ingenuity Pathways Analysis (IPA). Among the above 2-fold more upregulated genes in DS-iPS cells, 18 genes were on Hsa21. The expression of RUNX1 on Hsa21, a hematopoiesis-related gene, was significantly upregulated in DS-iPS cells. The high expressions of GATA1 and RUNX1 were also identified in 4-factor DS-iPS cells. Gene expression in blood cells differentiated from human induced pluripotent stem cells derived from patients with Down syndrome and healthy donor was measured in 12 days after induction of differentiation. Eight cell lines were used.
Project description:Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm of early childhood with a poor survival rate thus there is a requirement for improved treatment strategies. Induced pluripotent stem cells offer the ability to model disease and develop new treatment strategies. JMML is frequently associated with mutations in PTPN11. Children with Noonan syndrome, a development disorder, have an increased incidence of JMML associated with specific germline mutations in PTPN11. We undertook a proteomic assessment of myeloid cells derived from induced pluripotent stem cells obtained from Noonan syndrome patients with PTPN11 mutations, either associated or not associated with increased incidence of JMML. We report that the proteomic perturbations induced by the leukaemia-associated PTPN11 mutations are associated with TP53 and NF-ĸb signalling. We have previously shown that MYC is involved in the differential gene expression observed in Noonan syndrome patients associated with increased incidence of JMML. Thus, we employed drugs to target these pathways and demonstrate differentential effects on clonogenic hematopoietic cells derived from Noonan syndrome patients whom develop JMML and those who do not. Further, we demonstrated these small molecular inhibitors, JQ1 and CBL0137, preferentially extinguish primitive haematopoietic cells from sporadic JMML patients as opposed to cells from healthy individuals.
Project description:The goal of this study was to define molecular overlap between Down syndrome and Fragile X syndrome using human pluripotent stem cells (hPSCs) and in vitro derived glutamatergic neurons.
Project description:proteomes of the Human Embryonic Kidney (HEK) cells, the human induced pluripotent stem cells (hiPSCs), and the human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).
