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Organization of self-advantageous niche by neural stem/progenitor cells during development via autocrine VEGF-A under hypoxia
BACKGROUND: Tissue stem cells are confined within a special microenvironment called niche. Stem cells in such a niche are supplied with nutrients and contacted by other cells to maintain their characters and also to keep or expand their population size. Besides, oxygen concentration is a key factor...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9893632/ https://www.ncbi.nlm.nih.gov/pubmed/36726165 http://dx.doi.org/10.1186/s41232-022-00254-2 |
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author | Kashiwagi, Taichi Takazawa, Yuuki Kagawa, Tetsushi Taga, Tetsuya |
author_facet | Kashiwagi, Taichi Takazawa, Yuuki Kagawa, Tetsushi Taga, Tetsuya |
author_sort | Kashiwagi, Taichi |
collection | PubMed |
description | BACKGROUND: Tissue stem cells are confined within a special microenvironment called niche. Stem cells in such a niche are supplied with nutrients and contacted by other cells to maintain their characters and also to keep or expand their population size. Besides, oxygen concentration is a key factor for stem cell niche. Adult neural stem/progenitor cells (NSPCs) are known to reside in a hypoxic niche. Oxygen concentration levels are lower in fetal organs including brain than maternal organs. However, how fetal NSPCs adapt to the hypoxic environment during brain development, particularly before pial and periventricular vessels start to invade the telencephalon, has not fully been elucidated. METHODS: NSPCs were prepared from cerebral cortices of embryonic day (E) 11.5 or E14.5 mouse embryos and were enriched by 4-day incubation with FGF2. To evaluate NSPC numbers, neurosphere formation assay was performed. Sparsely plated NSPCs were cultured to form neurospheres under the hypoxic (1% O(2)) or normoxic condition. VEGF-A secreted from NSPCs in the culture medium was measured by ELISA. VEGF-A expression and Hif-1a in the developing brain was investigated by in situ hybridization and immunohistochemistry. RESULTS: Here we show that neurosphere formation of embryonic NSPCs is dramatically increased under hypoxia compared to normoxia. Vegf-A gene expression and its protein secretion were both up-regulated in the NSPCs under hypoxia. Either recombinant VEGF-A or conditioned medium of the hypoxic NSPC culture enhanced the neurosphere forming ability of normoxic NSPCs, which was attenuated by a VEGF-A signaling inhibitor. Furthermore, in the developing brain, VEGF-A was strongly expressed in the VZ where NSPCs are confined. CONCLUSIONS: We show that NSPCs secret VEGF-A in an autocrine fashion to efficiently maintain themselves under hypoxic developmental environment. Our results suggest that NSPCs have adaptive potential to respond to hypoxia to organize self-advantageous niche involving VEGF-A when the vascular system is immature. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41232-022-00254-2. |
format | Online Article Text |
id | pubmed-9893632 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-98936322023-02-03 Organization of self-advantageous niche by neural stem/progenitor cells during development via autocrine VEGF-A under hypoxia Kashiwagi, Taichi Takazawa, Yuuki Kagawa, Tetsushi Taga, Tetsuya Inflamm Regen Research Article BACKGROUND: Tissue stem cells are confined within a special microenvironment called niche. Stem cells in such a niche are supplied with nutrients and contacted by other cells to maintain their characters and also to keep or expand their population size. Besides, oxygen concentration is a key factor for stem cell niche. Adult neural stem/progenitor cells (NSPCs) are known to reside in a hypoxic niche. Oxygen concentration levels are lower in fetal organs including brain than maternal organs. However, how fetal NSPCs adapt to the hypoxic environment during brain development, particularly before pial and periventricular vessels start to invade the telencephalon, has not fully been elucidated. METHODS: NSPCs were prepared from cerebral cortices of embryonic day (E) 11.5 or E14.5 mouse embryos and were enriched by 4-day incubation with FGF2. To evaluate NSPC numbers, neurosphere formation assay was performed. Sparsely plated NSPCs were cultured to form neurospheres under the hypoxic (1% O(2)) or normoxic condition. VEGF-A secreted from NSPCs in the culture medium was measured by ELISA. VEGF-A expression and Hif-1a in the developing brain was investigated by in situ hybridization and immunohistochemistry. RESULTS: Here we show that neurosphere formation of embryonic NSPCs is dramatically increased under hypoxia compared to normoxia. Vegf-A gene expression and its protein secretion were both up-regulated in the NSPCs under hypoxia. Either recombinant VEGF-A or conditioned medium of the hypoxic NSPC culture enhanced the neurosphere forming ability of normoxic NSPCs, which was attenuated by a VEGF-A signaling inhibitor. Furthermore, in the developing brain, VEGF-A was strongly expressed in the VZ where NSPCs are confined. CONCLUSIONS: We show that NSPCs secret VEGF-A in an autocrine fashion to efficiently maintain themselves under hypoxic developmental environment. Our results suggest that NSPCs have adaptive potential to respond to hypoxia to organize self-advantageous niche involving VEGF-A when the vascular system is immature. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41232-022-00254-2. BioMed Central 2023-02-01 /pmc/articles/PMC9893632/ /pubmed/36726165 http://dx.doi.org/10.1186/s41232-022-00254-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Kashiwagi, Taichi Takazawa, Yuuki Kagawa, Tetsushi Taga, Tetsuya Organization of self-advantageous niche by neural stem/progenitor cells during development via autocrine VEGF-A under hypoxia |
title | Organization of self-advantageous niche by neural stem/progenitor cells during development via autocrine VEGF-A under hypoxia |
title_full | Organization of self-advantageous niche by neural stem/progenitor cells during development via autocrine VEGF-A under hypoxia |
title_fullStr | Organization of self-advantageous niche by neural stem/progenitor cells during development via autocrine VEGF-A under hypoxia |
title_full_unstemmed | Organization of self-advantageous niche by neural stem/progenitor cells during development via autocrine VEGF-A under hypoxia |
title_short | Organization of self-advantageous niche by neural stem/progenitor cells during development via autocrine VEGF-A under hypoxia |
title_sort | organization of self-advantageous niche by neural stem/progenitor cells during development via autocrine vegf-a under hypoxia |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9893632/ https://www.ncbi.nlm.nih.gov/pubmed/36726165 http://dx.doi.org/10.1186/s41232-022-00254-2 |
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