Organization of self-advantageous niche by neural stem/progenitor cells during development via autocrine VEGF-A under hypoxia
Abstract 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...
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | Inflammation and Regeneration |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s41232-022-00254-2 |
| _version_ | 1811171852176850944 |
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| author | Taichi Kashiwagi Yuuki Takazawa Tetsushi Kagawa Tetsuya Taga |
| author_facet | Taichi Kashiwagi Yuuki Takazawa Tetsushi Kagawa Tetsuya Taga |
| author_sort | Taichi Kashiwagi |
| collection | DOAJ |
| description | Abstract 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% O2) 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. |
| first_indexed | 2024-04-10T17:21:03Z |
| format | Article |
| id | doaj.art-e91ef7d8bc8d4186a1fcd3dd423bc6b6 |
| institution | Directory Open Access Journal |
| issn | 1880-8190 |
| language | English |
| last_indexed | 2024-04-10T17:21:03Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Inflammation and Regeneration |
| spelling | doaj.art-e91ef7d8bc8d4186a1fcd3dd423bc6b62023-02-05T12:06:52ZengBMCInflammation and Regeneration1880-81902023-02-0143111510.1186/s41232-022-00254-2Organization of self-advantageous niche by neural stem/progenitor cells during development via autocrine VEGF-A under hypoxiaTaichi Kashiwagi0Yuuki Takazawa1Tetsushi Kagawa2Tetsuya Taga3Department of Histology and Neuroanatomy, Tokyo Medical UniversityDepartment of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University (TMDU)Department of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University (TMDU)Department of Stem Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University (TMDU)Abstract 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% O2) 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.https://doi.org/10.1186/s41232-022-00254-2neural stem/progenitor cellsNSPC nicheself-organizationautocrinehypoxiavascular endothelial growth factor |
| spellingShingle | Taichi Kashiwagi Yuuki Takazawa Tetsushi Kagawa Tetsuya Taga Organization of self-advantageous niche by neural stem/progenitor cells during development via autocrine VEGF-A under hypoxia Inflammation and Regeneration neural stem/progenitor cells NSPC niche self-organization autocrine hypoxia vascular endothelial growth factor |
| 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 | neural stem/progenitor cells NSPC niche self-organization autocrine hypoxia vascular endothelial growth factor |
| url | https://doi.org/10.1186/s41232-022-00254-2 |
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