Synergistic Role of Igf2 and Dlk1 in Fetal Liver Development and Hematopoiesis in Bi-Maternal Mice

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概要

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• Mouse bi-maternal embryos (BMEs) that contain two haploid sets of genomes from non-growing (ng) and fully-grown (fg) oocytes develop to embryonic day (E) 13.5. However, the ng/fg BMEs never develop beyond E13.5 because of repression of the paternally expressed imprinted genes, Igf2 and Dlk1. The present study was conducted to address the issue of whether fetal hematopoietic disorder is involved in the restricted development of BMEs. FACS analysis revealed that the livers of ngwt/fg BMEs contained increased numbers of immature c-kit+/ter119- hematopoietic cells, were while the numbers of mature c-kit-/ter119+ hematopoietic cells were decreased. This finding was supported by histological observations. Quantitative gene expression analysis revealed that Igf2 and Dlk1 expression was repressed in the liver. To understand the role of paternally-methylated imprinted genes on chromosomes 7 and 12, particularly Igf2 and Dlk1, in fetal liver hematopoiesis, we constructed ngΔDch7/fg, ngΔch12/fg and ngΔDouble/fg BMEs using ng oocytes harboring deletion of differentially methylated regions at distal chromosomes 7 and/or 12. The ngΔch7/fg, ngΔch12/fg and ngΔDouble/fg BMEs, respectively, express Igf2, Dlk1 and both, and these embryos developed to term with specific phenotypes; the ngΔch7/fg and ngΔch12/fg BMEs develop to term with severe growth retardation, and the ngΔDouble/fg BMEs can survive to become normal female adults. By inducing Igf2 and Dlk1 expression, the proportions of mature and immature hematopoietic cells in the livers of the ngΔch7/fg, ngΔch12/fg and ngΔDouble/fg BMEs were considerably restored, and particularly in the ngΔDouble/fg BMEs, hematopoiesis occurred normally with appropriate expressions of the related genes. These data suggest that inappropriate expression of Igf2 and Dlk1 is involved in impaired fetal hematopoiesis.

• 日本繁殖生物学会の論文

著者

• WU Qiong

  Department of BioScience, Tokyo University of Agriculture

• KONO Tomohiro

  Department of BioScience, Tokyo University of Agriculture

• Wu Qiong

  Department Of Bioscience Tokyo University Of Agriculture

• Wu Qiong

  School Of Life Sciences Fudan University:research Center Of Natural Products Fudan University

• Wu Qiong

  Department Of Biological Sciences And Biotechnology Tsinghua University

• Kawahara Manabu

  Laboratory Of Animal Resource Development Faculty Of Agriculture Saga University

• KAWAHARA Manabu

  Department of BioScience, Tokyo University of Agriculture

• Kono Tomohiro

  Department Of Animal Science Tokyo University Of Agriculture

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