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Induced pluripotent stem cells derived from the developing striatum as a potential donor source for cell replacement therapy for Huntington disease
BACKGROUND: Cell replacement therapy (CRT) for Huntington disease (HD) requires a source of striatal (STR) progenitors capable of restoring the function lost due to STR degeneration. Authentic STR progenitors can be collected from the fetal putative striatum, or whole ganglionic eminence (WGE), but...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822401/ https://www.ncbi.nlm.nih.gov/pubmed/33246883 http://dx.doi.org/10.1016/j.jcyt.2020.06.001 |
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author | Choompoo, Narawadee Bartley, Oliver J.M. Precious, Sophie V. Vinh, Ngoc-nga Schnell, Christian Garcia, Ana Roberton, Victoria H. Williams, Nigel M. Kemp, Paul J. Kelly, Claire M. Rosser, Anne E. |
author_facet | Choompoo, Narawadee Bartley, Oliver J.M. Precious, Sophie V. Vinh, Ngoc-nga Schnell, Christian Garcia, Ana Roberton, Victoria H. Williams, Nigel M. Kemp, Paul J. Kelly, Claire M. Rosser, Anne E. |
author_sort | Choompoo, Narawadee |
collection | PubMed |
description | BACKGROUND: Cell replacement therapy (CRT) for Huntington disease (HD) requires a source of striatal (STR) progenitors capable of restoring the function lost due to STR degeneration. Authentic STR progenitors can be collected from the fetal putative striatum, or whole ganglionic eminence (WGE), but these tissues remain impractical for widespread clinical application, and alternative donor sources are required. Here we begin exploring the possibility that induced pluripotent stem cells (iPSC) derived from WGE may retain an epigenetic memory of their tissue of origin, which could enhance their ability to differentiate into STR cells. RESULTS: We generate four iPSC lines from human WGE (hWGE) and establish that they have a capacity similar to human embryonic stem cells with regard to their ability to differentiate toward an STR phenotype, as measured by expression and demethylation of key STR genes, while maintaining an overall different methylome. Finally, we demonstrate that these STR-differentiated hWGE iPSCs share characteristics with hWGE (i.e., authentic STR tissues) both in vitro and following transplantation into an HD model. Overall, iPSCs derived from human WGE show promise as a donor source for CRT for HD. |
format | Online Article Text |
id | pubmed-7822401 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-78224012021-02-01 Induced pluripotent stem cells derived from the developing striatum as a potential donor source for cell replacement therapy for Huntington disease Choompoo, Narawadee Bartley, Oliver J.M. Precious, Sophie V. Vinh, Ngoc-nga Schnell, Christian Garcia, Ana Roberton, Victoria H. Williams, Nigel M. Kemp, Paul J. Kelly, Claire M. Rosser, Anne E. Cytotherapy Short Report BACKGROUND: Cell replacement therapy (CRT) for Huntington disease (HD) requires a source of striatal (STR) progenitors capable of restoring the function lost due to STR degeneration. Authentic STR progenitors can be collected from the fetal putative striatum, or whole ganglionic eminence (WGE), but these tissues remain impractical for widespread clinical application, and alternative donor sources are required. Here we begin exploring the possibility that induced pluripotent stem cells (iPSC) derived from WGE may retain an epigenetic memory of their tissue of origin, which could enhance their ability to differentiate into STR cells. RESULTS: We generate four iPSC lines from human WGE (hWGE) and establish that they have a capacity similar to human embryonic stem cells with regard to their ability to differentiate toward an STR phenotype, as measured by expression and demethylation of key STR genes, while maintaining an overall different methylome. Finally, we demonstrate that these STR-differentiated hWGE iPSCs share characteristics with hWGE (i.e., authentic STR tissues) both in vitro and following transplantation into an HD model. Overall, iPSCs derived from human WGE show promise as a donor source for CRT for HD. Elsevier 2021-02 /pmc/articles/PMC7822401/ /pubmed/33246883 http://dx.doi.org/10.1016/j.jcyt.2020.06.001 Text en © 2020 International Society for Cell & Gene Therapy. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Short Report Choompoo, Narawadee Bartley, Oliver J.M. Precious, Sophie V. Vinh, Ngoc-nga Schnell, Christian Garcia, Ana Roberton, Victoria H. Williams, Nigel M. Kemp, Paul J. Kelly, Claire M. Rosser, Anne E. Induced pluripotent stem cells derived from the developing striatum as a potential donor source for cell replacement therapy for Huntington disease |
title | Induced pluripotent stem cells derived from the developing striatum as a potential donor source for cell replacement therapy for Huntington disease |
title_full | Induced pluripotent stem cells derived from the developing striatum as a potential donor source for cell replacement therapy for Huntington disease |
title_fullStr | Induced pluripotent stem cells derived from the developing striatum as a potential donor source for cell replacement therapy for Huntington disease |
title_full_unstemmed | Induced pluripotent stem cells derived from the developing striatum as a potential donor source for cell replacement therapy for Huntington disease |
title_short | Induced pluripotent stem cells derived from the developing striatum as a potential donor source for cell replacement therapy for Huntington disease |
title_sort | induced pluripotent stem cells derived from the developing striatum as a potential donor source for cell replacement therapy for huntington disease |
topic | Short Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822401/ https://www.ncbi.nlm.nih.gov/pubmed/33246883 http://dx.doi.org/10.1016/j.jcyt.2020.06.001 |
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