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The role of C/EBPa on the development of monocyte subsets
- Abstract
- The integrity of the hematopoietic system depends on a large number of blood cell lineages being continuously replenished from a rare population of pluripotent heatopoietic stem cells(HSC), representing a paradigm for how multilineage diversity can be achieved from a common stem cell through lineage commitment and subsequent differentiation.
Monocytes are mononuclear cells and represent about 10% of leukocytes in human blood and 4% of leukocytes in mouse blood. The best known function of monocytes is their role as accessory cells, which link inflammation and the innate defense system against microorganisms to adaptive immune response.
Many factors are involved in monocyte differentiation like PU.1, IRF8, KLF-4, MafB, c-maf and C/EBPalpha. C/EBPalpha (CCAAT/enhancer binding protein alpha) is a basic region-leucine zipper transcription factor and indispensable for formation of mature neutrophils and eosinophils. It is expressed at low levels in HSC, and is up-regulated to its highest levels in GMP(granulocyte/monocyte progenitors), whereas it is not expressed in precursors of lymphoid cells and is downregulated as CMP differentiate to MEP(megakaryocyte/erythrocyte progenitors). Mice-studies indicate that C/EBPalpha is essential for transition of CMP to GMP.
We hypothesize that C/EBPalpha positive and C/EBPalpha negative monocytes represent distinct subgroups of monocytes, which also differ in their function. In addition, we speculate that they are derived from different progenitors. To experimentally approach this hypothesis we want to use the C/EBPalphaCRE EYFP reporter mouse model.
- Project Leader:
- Wölfler Albert
- Duration:
- 01.08.2009-31.07.2013
- Type of Research
- basic research
- Staff
- Wölfler, Albert, Project Leader
- Fried, Isabella, Co-worker
- Schlacher, Angelika, Co-worker
- MUG Research Units
- Division of Haematology