title: Localized SCF and IGF-1 secretion enhances erythropoiesis in the spleen of murine embryos.
abstract: Fetal spleen is a major hematopoietic site prior to initiation of bone marrow hematopoiesis. Morphologic analysis suggested erythropoietic activity in fetal spleen, but it remained unclear how erythropoiesis was regulated. To address this question, we performed flow cytometric analysis and observed that the number of spleen erythroid cells increased 18.6-fold from 16.5 to 19.5 days post-coitum (dpc). Among erythropoietic cytokines, SCF and IGF-1 were primarily expressed in hematopoietic, endothelial and mesenchymal-like fetal spleen cells. Cultures treated with SCF and/or IGF-1R inhibitors showed significantly decreased CD45-c-Kit-CD71+/-Ter119+ erythroid cells and downregulated Gata1, Klf1 and β-major globin expression. Administration of these inhibitors to pregnant mice significantly decreased the number of CD45-c-Kit-CD71+/-Ter119+ cells and downregulated β-major globin gene expression in embryos derived from these mice. We conclude that fetal spleen is a major erythropoietic site where endothelial and mesenchymal-like cells primarily accelerate erythropoietic activity through SCF and IGF-1 secretion.
authors.affiliation: Department of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582 Japan Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor Darul Ehsan, Malaysia.
authors.forename: Keai Sinn
authors.initials: KS
authors.lastname: Tan
authors.affiliation: Department of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582 Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582 Japan.
authors.forename: Kasem
authors.initials: K
authors.lastname: Kulkeaw
authors.affiliation: Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka 812-8582 Japan Department of Clinical Study, Center for Advanced Medical Innovation, Kyushu University, Fukuoka 812-8582 Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor Darul Ehsan, Malaysia.
authors.forename: Mei I
authors.initials: MI
authors.lastname: Lai
authors.affiliation: Department of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582 Japan Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka 812-8582 Japan Department of Clinical Study, Center for Advanced Medical Innovation, Kyushu University, Fukuoka 812-8582 Japan ds-mons@yb3.so-net.ne.jp.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sugiyama
keywords: Erythropoiesis; Fetal spleen; Niche, Cytokines