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Localized SCF and IGF-1 secretion enhances erythropoiesis in the spleen of murine embryos

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...

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Autores principales: Tan, Keai Sinn, Inoue, Tomoko, Kulkeaw, Kasem, Tanaka, Yuka, Lai, Mei I, Sugiyama, Daisuke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434811/
https://www.ncbi.nlm.nih.gov/pubmed/25887124
http://dx.doi.org/10.1242/bio.201410686
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author Tan, Keai Sinn
Inoue, Tomoko
Kulkeaw, Kasem
Tanaka, Yuka
Lai, Mei I
Sugiyama, Daisuke
author_facet Tan, Keai Sinn
Inoue, Tomoko
Kulkeaw, Kasem
Tanaka, Yuka
Lai, Mei I
Sugiyama, Daisuke
author_sort Tan, Keai Sinn
collection PubMed
description 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.
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spelling pubmed-44348112015-06-11 Localized SCF and IGF-1 secretion enhances erythropoiesis in the spleen of murine embryos Tan, Keai Sinn Inoue, Tomoko Kulkeaw, Kasem Tanaka, Yuka Lai, Mei I Sugiyama, Daisuke Biol Open Research Article 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. The Company of Biologists 2015-04-17 /pmc/articles/PMC4434811/ /pubmed/25887124 http://dx.doi.org/10.1242/bio.201410686 Text en © 2015. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Tan, Keai Sinn
Inoue, Tomoko
Kulkeaw, Kasem
Tanaka, Yuka
Lai, Mei I
Sugiyama, Daisuke
Localized SCF and IGF-1 secretion enhances erythropoiesis in the spleen of murine embryos
title Localized SCF and IGF-1 secretion enhances erythropoiesis in the spleen of murine embryos
title_full Localized SCF and IGF-1 secretion enhances erythropoiesis in the spleen of murine embryos
title_fullStr Localized SCF and IGF-1 secretion enhances erythropoiesis in the spleen of murine embryos
title_full_unstemmed Localized SCF and IGF-1 secretion enhances erythropoiesis in the spleen of murine embryos
title_short Localized SCF and IGF-1 secretion enhances erythropoiesis in the spleen of murine embryos
title_sort localized scf and igf-1 secretion enhances erythropoiesis in the spleen of murine embryos
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434811/
https://www.ncbi.nlm.nih.gov/pubmed/25887124
http://dx.doi.org/10.1242/bio.201410686
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