c-Maf plays a crucial role for the definitive erythropoiesis that accompanies erythroblastic island formation in the fetal liver.
Blood, 2011/8/04;118(5):1374-85.
Kusakabe M[1], Hasegawa K, Hamada M, Nakamura M, Ohsumi T, Suzuki H, Tran MT, Kudo T, Uchida K, Ninomiya H, Chiba S, Takahashi S
Affiliations
PMID: 21628412DOI: 10.1182/blood-2010-08-300400
Impact factor: 25.476
Abstract
c-Maf is one of the large Maf (musculoaponeurotic fibrosarcoma) transcription factors that belong to the activated protein-1 super family of basic leucine zipper proteins. Despite its overexpression in hematologic malignancies, the physiologic roles c-Maf plays in normal hematopoiesis have been largely unexplored. On a C57BL/6J background, c-Maf(-/-) embryos succumbed from severe erythropenia between embryonic day (E) 15 and E18. Flow cytometric analysis of fetal liver cells showed that the mature erythroid compartments were significantly reduced in c-Maf(-/-) embryos compared with c-Maf(+/+) littermates. Interestingly, the CFU assay indicated there was no significant difference between c-Maf(+/+) and c-Maf(-/-) fetal liver cells in erythroid colony counts. This result indicated that impaired definitive erythropoiesis in c-Maf(-/-) embryos is because of a non-cell-autonomous effect, suggesting a defective erythropoietic microenvironment in the fetal liver. As expected, the number of erythroblasts surrounding the macrophages in erythroblastic islands was significantly reduced in c-Maf(-/-) embryos. Moreover, decreased expression of VCAM-1 was observed in c-Maf(-/-) fetal liver macrophages. In conclusion, these results strongly suggest that c-Maf is crucial for definitive erythropoiesis in fetal liver, playing an important role in macrophages that constitute erythroblastic islands.
MeSH terms
Animals; Cell Communication; Cell Movement; Cell Proliferation; Embryo, Mammalian; Erythroblasts; Erythropoiesis; Fetus; Gene Expression Profiling; Liver; Macrophages; Mice; Mice, Inbred C57BL; Mice, Knockout; Microarray Analysis; Proto-Oncogene Proteins c-maf
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