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Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells
BACKGROUND: 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 associa...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3224699/ https://www.ncbi.nlm.nih.gov/pubmed/19682396 http://dx.doi.org/10.1186/1471-2202-10-97 |
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author | Woo, Sun-Mi Kim, Janghwan Han, Hyo-Won Chae, Jung-Il Son, Mi-Young Cho, Sunwha Chung, Hyung-Min Han, Yong-Mahn Kang, Yong-Kook |
author_facet | Woo, Sun-Mi Kim, Janghwan Han, Hyo-Won Chae, Jung-Il Son, Mi-Young Cho, Sunwha Chung, Hyung-Min Han, Yong-Mahn Kang, Yong-Kook |
author_sort | Woo, Sun-Mi |
collection | PubMed |
description | BACKGROUND: 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. RESULTS: From hESCs, we derived NESs, the in-vitro 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 in-vivo-derived neuroprogenitors, is active in these hESC-derived NESs, similar to their in-vivo 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. CONCLUSION: 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 in-vitro model for in-vivo neurogenesis. |
format | Online Article Text |
id | pubmed-3224699 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-32246992011-11-28 Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells Woo, Sun-Mi Kim, Janghwan Han, Hyo-Won Chae, Jung-Il Son, Mi-Young Cho, Sunwha Chung, Hyung-Min Han, Yong-Mahn Kang, Yong-Kook BMC Neurosci Research Article BACKGROUND: 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. RESULTS: From hESCs, we derived NESs, the in-vitro 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 in-vivo-derived neuroprogenitors, is active in these hESC-derived NESs, similar to their in-vivo 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. CONCLUSION: 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 in-vitro model for in-vivo neurogenesis. BioMed Central 2009-08-17 /pmc/articles/PMC3224699/ /pubmed/19682396 http://dx.doi.org/10.1186/1471-2202-10-97 Text en Copyright ©2009 Woo et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Woo, Sun-Mi Kim, Janghwan Han, Hyo-Won Chae, Jung-Il Son, Mi-Young Cho, Sunwha Chung, Hyung-Min Han, Yong-Mahn Kang, Yong-Kook Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells |
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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3224699/ https://www.ncbi.nlm.nih.gov/pubmed/19682396 http://dx.doi.org/10.1186/1471-2202-10-97 |
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