Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells
<p>Abstract</p> <p>Background</p> <p>Studies have provided important findings about the roles of Notch signaling in neural development. Unfortunately, however, most of these studies have investigated the neural stem cells (NSCs) of mice or other laboratory animals rathe...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2009-08-01
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| Series: | BMC Neuroscience |
| Online Access: | http://www.biomedcentral.com/1471-2202/10/97 |
| _version_ | 1818689105352982528 |
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| author | Chung Hyung-Min Cho Sunwha Son Mi-Young Chae Jung-Il Han Hyo-Won Kim Janghwan Woo Sun-Mi Han Yong-Mahn Kang Yong-Kook |
| author_facet | Chung Hyung-Min Cho Sunwha Son Mi-Young Chae Jung-Il Han Hyo-Won Kim Janghwan Woo Sun-Mi Han Yong-Mahn Kang Yong-Kook |
| author_sort | Chung Hyung-Min |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Studies have provided important findings about the roles of Notch signaling in neural development. Unfortunately, however, most of these studies have investigated the neural stem cells (NSCs) of mice or other laboratory animals rather than humans, mainly owing to the difficulties associated with obtaining human brain samples. It prompted us to focus on neuroectodermal spheres (NESs) which are derived from human embryonic stem cell (hESC) and densely inhabited by NSCs. We here investigated the role of Notch signaling with the hESC-derived NESs.</p> <p>Results</p> <p>From hESCs, we derived NESs, the <it>in-vitro </it>version of brain-derived neurospheres. NES formation was confirmed by increased levels of various NSC marker genes and the emergence of rosette structures in which neuroprogenitors are known to reside. We found that Notch signaling, which maintains stem cell characteristics of <it>in-vivo</it>-derived neuroprogenitors, is active in these hESC-derived NESs, similar to their <it>in-vivo </it>counterpart. Expression levels of Notch signaling molecules such as NICD, DLLs, JAG1, HES1 and HES5 were increased in the NESs. Inhibition of the Notch signaling by a γ-secretase inhibitor reduced rosette structures, expression levels of NSC marker genes and proliferation potential in the NESs, and, if combined with withdrawal of growth factors, triggered differentiation toward neurons.</p> <p>Conclusion</p> <p>Our results indicate that the hESC-derived NESs, which share biochemical features with brain-derived neurospheres, maintain stem cell characteristics mainly through Notch signaling, which suggests that the hESC-derived NESs could be an <it>in-vitro </it>model for <it>in-vivo </it>neurogenesis.</p> |
| first_indexed | 2024-12-17T12:04:49Z |
| format | Article |
| id | doaj.art-42bc1c95cd6e42058956f7b843e7f17e |
| institution | Directory Open Access Journal |
| issn | 1471-2202 |
| language | English |
| last_indexed | 2024-12-17T12:04:49Z |
| publishDate | 2009-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neuroscience |
| spelling | doaj.art-42bc1c95cd6e42058956f7b843e7f17e2022-12-21T21:49:41ZengBMCBMC Neuroscience1471-22022009-08-011019710.1186/1471-2202-10-97Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cellsChung Hyung-MinCho SunwhaSon Mi-YoungChae Jung-IlHan Hyo-WonKim JanghwanWoo Sun-MiHan Yong-MahnKang Yong-Kook<p>Abstract</p> <p>Background</p> <p>Studies have provided important findings about the roles of Notch signaling in neural development. Unfortunately, however, most of these studies have investigated the neural stem cells (NSCs) of mice or other laboratory animals rather than humans, mainly owing to the difficulties associated with obtaining human brain samples. It prompted us to focus on neuroectodermal spheres (NESs) which are derived from human embryonic stem cell (hESC) and densely inhabited by NSCs. We here investigated the role of Notch signaling with the hESC-derived NESs.</p> <p>Results</p> <p>From hESCs, we derived NESs, the <it>in-vitro </it>version of brain-derived neurospheres. NES formation was confirmed by increased levels of various NSC marker genes and the emergence of rosette structures in which neuroprogenitors are known to reside. We found that Notch signaling, which maintains stem cell characteristics of <it>in-vivo</it>-derived neuroprogenitors, is active in these hESC-derived NESs, similar to their <it>in-vivo </it>counterpart. Expression levels of Notch signaling molecules such as NICD, DLLs, JAG1, HES1 and HES5 were increased in the NESs. Inhibition of the Notch signaling by a γ-secretase inhibitor reduced rosette structures, expression levels of NSC marker genes and proliferation potential in the NESs, and, if combined with withdrawal of growth factors, triggered differentiation toward neurons.</p> <p>Conclusion</p> <p>Our results indicate that the hESC-derived NESs, which share biochemical features with brain-derived neurospheres, maintain stem cell characteristics mainly through Notch signaling, which suggests that the hESC-derived NESs could be an <it>in-vitro </it>model for <it>in-vivo </it>neurogenesis.</p>http://www.biomedcentral.com/1471-2202/10/97 |
| spellingShingle | Chung Hyung-Min Cho Sunwha Son Mi-Young Chae Jung-Il Han Hyo-Won Kim Janghwan Woo Sun-Mi Han Yong-Mahn Kang Yong-Kook Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells BMC Neuroscience |
| title | Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells |
| title_full | Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells |
| title_fullStr | Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells |
| title_full_unstemmed | Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells |
| title_short | Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells |
| title_sort | notch signaling is required for maintaining stem cell features of neuroprogenitor cells derived from human embryonic stem cells |
| url | http://www.biomedcentral.com/1471-2202/10/97 |
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