title: Embryonic regulation of the mouse erythropoietic niche and its clinical application.
abstract: Erythropoiesis has classically been described as occurring in two waves: first primitive and then definitive erythropoiesis. In the mouse embryo, definitive erythropoiesis begins in the yolk sac and then shifts to the liver, spleen, and bone marrow. The fetal liver serves as the primary organ for erythroid cell expansion and maturation at mid-gestation and its mechanisms have been well investigated with special attention to niche cells expressing cytokines such as SCF, TPO and IGF2. Previously, our group reported that DLK1(+) hepatoblasts support fetal liver hematopoiesis, particularly erythropoiesis, through EPO, SCF and matrix secretion. Loss of DLK1(+) hepatoblasts in Map2k4(-/-) mouse embryos resulted in decreased numbers of hematopoietic cells in the fetal liver. When sorted DLK1(+) hepatoblasts were further analyzed by microarray, several genes encoding proteinases and peptidases were highly expressed in DLK1(+) hepatoblasts. Based on the hypothesis that high molecular weight proteins are digested into small peptides that may regulate hematopoiesis, we screened out peptides, and identified KS-13 (PCT/JP2010/067011). Both KS-13 and modified KS-13, known as SL-13R, proliferate and increase the number of hematopoietic stem/progenitors from human cord blood cells in vitro. We hereby present our findings on the extrinsic regulation of embryonic erythropoiesis with special attention to niche cells, identification of niche-derived peptides, and implications for future hematotherapy.
authors: Department of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu University.
authors: Daisuke
authors: D
authors: Sugiyama
authors: Yuka
authors: Y
authors: Tanaka
authors: Ayako
authors: A
authors: Yumine
authors: Naoko
authors: N
authors: Kojima
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D004920:Erythropoiesis; D006801:Humans; D051379:Mice; D009928:Organ Specificity; D010455:Peptides / Q000378:metabolism
chemical_list: D010455:Peptides