@article{525d5a197639499a8803b37894a1e683,
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.",
author = "Tan, {Keai Sinn} and Tomoko Inoue and Kasem Kulkeaw and Yuka Tanaka and Lai, {Mei I.} and Daisuke Sugiyama",
note = "Funding Information: We thank Ms. Wai Feng Lim and Chiyo Mizuochi-Yanagi for discussion and technical support, Drs. Yoichi Nakanishi, Elizabeth George and Syahrilnizam Abdullah for continuous encouragement and Dr. Elise Lamar for critical reading of the manuscript. This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology; the Ministry of Health, Labor and Welfare; the Japan Society for the Promotion of Science; the Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care; the Institute of Molecular Embryology and Genetics; and the International Research Fund for Subsidy of Kyushu University School of Medicine Alumni. Keai Sinn Tan is a recipient of a scholarship from the Tokyo Biochemical Research Foundation, Japan, and a MyPhD scholarship from Ministry of Higher Education (MOHE), Malaysia. Funding Information: This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology; the Ministry of Health, Labor and Welfare; the Japan Society for the Promotion of Science; the Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care; the Institute of Molecular Embryology and Genetics; and the International Research Fund for Subsidy of Kyushu University School of Medicine Alumni. Keai Sinn Tan is a recipient of a scholarship from the Tokyo Biochemical Research Foundation, Japan, and a MyPhD scholarship from Ministry of Higher Education (MOHE), Malaysia. Publisher Copyright: {\textcopyright} 2015, The Company of Biologists Ltd. All rights reserved. Copyright: Copyright 2016 Elsevier B.V., All rights reserved.",
year = "2015",
month = may,
day = "15",
doi = "10.1242/bio.201410686",
language = "English",
volume = "4",
pages = "596--607",
journal = "Biology Open",
issn = "2046-6390",
publisher = "Company of Biologists Ltd",
number = "5",
}