Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Introduction of genes for cytokine receptors into hematopoietic stem/progenitor cells (HSC/HPC) may be of clinical use in the future. We recently reported that retroviral-mediated transduction of either the human erythropoietin receptor (hEpoR) or interleukin-9 receptor (hIL-9R) genes into highly purified HSC/HPC from cord blood (CB) resulted in increased numbers of detectable cytokine-responsive erythroid progenitors (burst-forming units-erythroid [BFU-E]). In the present study, we evaluated if this increase could be further enhanced by cotransducing both these genes into single isolated HSC/HPC. Single CD34++CD33-or low-expressing cells from CB were transduced with viral supernatant containing the hEpoR or hIL-9R genes or cotransduced with both genes. In the presence of Steel factor (SLF), interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin (Epo), and IL-9, the numbers of erythroid colonies formed were significantly increased after transduction of cells with either the hIL-9R or hEpoR gene compared to mock-transduced cells. This increase was significantly enhanced in cells cotransduced with both genes compared with either gene alone. Integration and expression of both genes was confirmed by polymerase chain reaction (PCR) and reverse-transcriptase (RT)-PCR analysis, respectively. The data demonstrate that myeloid progenitors can be transduced at the single-cell level with both hEpoR and hIL-9R genes with resultant enhanced proliferation of these progenitors in the erythroid lineage by combinations of cytokines including Epo and IL-9.
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PMID:Influence of retroviral-mediated gene transduction of both the recombinant human erythropoietin receptor and interleukin-9 receptor genes into single CD34++CD33-or low cord blood cells on cytokine-stimulated erythroid colony formation. 864 64

Understanding of the mechanism for myeloid differentiation provides important insights into the hematopoietic developmental processes. By using an ESC-derived myeloid progenitor cell model, we found that CSF2/GM-CSF triggered macrophage differentiation and activation of the MTOR signaling pathway. Activation or inhibition of the MTOR signaling enhanced or attenuated macrophage differentiation, respectively, suggesting a critical function. We further showed that macroautophagy/autophagy was inhibited with the addition of CSF2. Furthermore, pharmacological inhibition and genetic modification of autophagy enhanced macrophage differentiation and rescued the inhibitory effect on differentiation caused by MTOR inhibition. Thus, the MTOR signaling pathway regulates macrophage differentiation of myeloid progenitors by inhibiting autophagy. Our results provide new insights into the mechanisms for myeloid differentiation and may prove useful for therapeutic applications of hematopoietic and myeloid progenitor cells. Abbreviations: 2-DG: 2-deoxy-D-glucose; ADGRE1/F4/80: adhesion G protein-coupled receptor E1; BM: bone marrow; CQ: chloroquine; ECAR: extracellular acidification rate; ESC: embryonic stem cell; CSF2/GM-CSF: colony stimulating factor 2; CSF3/G-CSF: colony stimulating factor 3; HPC: hematopoietic progenitor cell; ITGAM/CD11b: integrin alpha M; LPS: lipopolysaccharide; MFI: median fluorescence intensity; MTOR: mechanistic target of rapamycin kinase; RPS6KB1/p70S6K1: ribosomal protein S6 kinase, polypeptide 1; shRNA: short hairpin RNA; SQSTM1/p62: sequestosome 1.
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PMID:The MTOR signaling pathway regulates macrophage differentiation from mouse myeloid progenitors by inhibiting autophagy. 3072 90