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FDB1_GM-CSFTyr577_Receptor_Mutant_Factorial_Time_Course_Study

ABSTRACT: To understand better the mechanisms controlling the balance between proliferation and and differentiation during myelopoiesis we have utilized teh bi-potent FDB1 myeloid cell line which differentiates to granulocytes and macrophages in response to GM-CSF and thus provides a dissectable model to analyse the switch between growth and differentiation. This was further studied using this cell line in which a second site mutation Y577F had been generated. A factorial time-course design between the two cell lines and over time, combined with linear modelling and geneset enrichment analysis identified the expression changes associated with the switch between granulocyte differentiation and macrophage differentiation. We observed that a single intracellular tyrosine residue (Tyr577) mediates the granulocyte fate decision. The loss of granulocyte differentiation and enhanced macrophage differentiation observed in this second site mutant is associated with accumulation of Beta-Catenin and activation of Tcf4 and other Wnt Target genes.

ORGANISM(S): Mus musculus

PROVIDER: GSE25857 | GEO | 2010/12/07

SECONDARY ACCESSION(S): PRJNA135733

REPOSITORIES: GEO

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FDB1_GM-CSFTyr577_Receptor_Mutant_Factorial_Time_Course_Study

Project description:To understand better the mechanisms controlling the balance between proliferation and and differentiation during myelopoiesis we have utilized teh bi-potent FDB1 myeloid cell line which differentiates to granulocytes and macrophages in response to GM-CSF and thus provides a dissectable model to analyse the switch between growth and differentiation. This was further studied using this cell line in which a second site mutation Y577F had been generated. A factorial time-course design between the two cell lines and over time, combined with linear modelling and geneset enrichment analysis identified the expression changes associated with the switch between granulocyte differentiation and macrophage differentiation. We observed that a single intracellular tyrosine residue (Tyr577) mediates the granulocyte fate decision. The loss of granulocyte differentiation and enhanced macrophage differentiation observed in this second site mutant is associated with accumulation of Beta-Catenin and activation of Tcf4 and other Wnt Target genes. Factorial design. First Factor was cell type with levels FDB1 expressing FI-Delta receptor mutant and FDB1 expressing FI-Delta Y577F receptor mutant. Second factor is time with levels 0 and 72 hours. Two biological replicates wre prepared for each cell line and comparions were perfomed for each cell line and directly between cell lines at 0 and 72hs. Additional dye swaps were done with FI Delta and FIDelta Y577F at 0h and the FI Delta 0-72h comparison.

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