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Postmortem Human Dura Mater Cells Exhibit Phenotypic, Transcriptomic and Genetic Abnormalities that Impact their Use for Disease Modeling
Patient-derived cells hold great promise for precision medicine approaches in human health. Human dermal fibroblasts have been a major source of cells for reprogramming and differentiating into specific cell types for disease modeling. Postmortem human dura mater has been suggested as a primary sour...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9622518/ https://www.ncbi.nlm.nih.gov/pubmed/35809166 http://dx.doi.org/10.1007/s12015-022-10416-x |
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author | Argouarch, Andrea R. Schultz, Nina Yang, Andrew C. Jang, Yeongjun Garcia, Kristle Cosme, Celica G. Corrales, Christian I. Nana, Alissa L. Karydas, Anna M. Spina, Salvatore Grinberg, Lea T. Miller, Bruce Wyss-Coray, Tony Abyzov, Alexej Goodarzi, Hani Seeley, William W. Kao, Aimee W. |
author_facet | Argouarch, Andrea R. Schultz, Nina Yang, Andrew C. Jang, Yeongjun Garcia, Kristle Cosme, Celica G. Corrales, Christian I. Nana, Alissa L. Karydas, Anna M. Spina, Salvatore Grinberg, Lea T. Miller, Bruce Wyss-Coray, Tony Abyzov, Alexej Goodarzi, Hani Seeley, William W. Kao, Aimee W. |
author_sort | Argouarch, Andrea R. |
collection | PubMed |
description | Patient-derived cells hold great promise for precision medicine approaches in human health. Human dermal fibroblasts have been a major source of cells for reprogramming and differentiating into specific cell types for disease modeling. Postmortem human dura mater has been suggested as a primary source of fibroblasts for in vitro modeling of neurodegenerative diseases. Although fibroblast-like cells from human and mouse dura mater have been previously described, their utility for reprogramming and direct differentiation protocols has not been fully established. In this study, cells derived from postmortem dura mater are directly compared to those from dermal biopsies of living subjects. In two instances, we have isolated and compared dermal and dural cell lines from the same subject. Notably, striking differences were observed between cells of dermal and dural origin. Compared to dermal fibroblasts, postmortem dura mater-derived cells demonstrated different morphology, slower growth rates, and a higher rate of karyotype abnormality. Dura mater-derived cells also failed to express fibroblast protein markers. When dermal fibroblasts and dura mater-derived cells from the same subject were compared, they exhibited highly divergent gene expression profiles that suggest dura mater cells originated from a mixed mural lineage. Given their postmortem origin, somatic mutation signatures of dura mater-derived cells were assessed and suggest defective DNA damage repair. This study argues for rigorous karyotyping of postmortem derived cell lines and highlights limitations of postmortem human dura mater-derived cells for modeling normal biology or disease-associated pathobiology. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12015-022-10416-x. |
format | Online Article Text |
id | pubmed-9622518 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-96225182022-11-02 Postmortem Human Dura Mater Cells Exhibit Phenotypic, Transcriptomic and Genetic Abnormalities that Impact their Use for Disease Modeling Argouarch, Andrea R. Schultz, Nina Yang, Andrew C. Jang, Yeongjun Garcia, Kristle Cosme, Celica G. Corrales, Christian I. Nana, Alissa L. Karydas, Anna M. Spina, Salvatore Grinberg, Lea T. Miller, Bruce Wyss-Coray, Tony Abyzov, Alexej Goodarzi, Hani Seeley, William W. Kao, Aimee W. Stem Cell Rev Rep Article Patient-derived cells hold great promise for precision medicine approaches in human health. Human dermal fibroblasts have been a major source of cells for reprogramming and differentiating into specific cell types for disease modeling. Postmortem human dura mater has been suggested as a primary source of fibroblasts for in vitro modeling of neurodegenerative diseases. Although fibroblast-like cells from human and mouse dura mater have been previously described, their utility for reprogramming and direct differentiation protocols has not been fully established. In this study, cells derived from postmortem dura mater are directly compared to those from dermal biopsies of living subjects. In two instances, we have isolated and compared dermal and dural cell lines from the same subject. Notably, striking differences were observed between cells of dermal and dural origin. Compared to dermal fibroblasts, postmortem dura mater-derived cells demonstrated different morphology, slower growth rates, and a higher rate of karyotype abnormality. Dura mater-derived cells also failed to express fibroblast protein markers. When dermal fibroblasts and dura mater-derived cells from the same subject were compared, they exhibited highly divergent gene expression profiles that suggest dura mater cells originated from a mixed mural lineage. Given their postmortem origin, somatic mutation signatures of dura mater-derived cells were assessed and suggest defective DNA damage repair. This study argues for rigorous karyotyping of postmortem derived cell lines and highlights limitations of postmortem human dura mater-derived cells for modeling normal biology or disease-associated pathobiology. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12015-022-10416-x. Springer US 2022-07-09 2022 /pmc/articles/PMC9622518/ /pubmed/35809166 http://dx.doi.org/10.1007/s12015-022-10416-x Text en © The Author(s) 2022 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 | Article Argouarch, Andrea R. Schultz, Nina Yang, Andrew C. Jang, Yeongjun Garcia, Kristle Cosme, Celica G. Corrales, Christian I. Nana, Alissa L. Karydas, Anna M. Spina, Salvatore Grinberg, Lea T. Miller, Bruce Wyss-Coray, Tony Abyzov, Alexej Goodarzi, Hani Seeley, William W. Kao, Aimee W. Postmortem Human Dura Mater Cells Exhibit Phenotypic, Transcriptomic and Genetic Abnormalities that Impact their Use for Disease Modeling |
title | Postmortem Human Dura Mater Cells Exhibit Phenotypic, Transcriptomic and Genetic Abnormalities that Impact their Use for Disease Modeling |
title_full | Postmortem Human Dura Mater Cells Exhibit Phenotypic, Transcriptomic and Genetic Abnormalities that Impact their Use for Disease Modeling |
title_fullStr | Postmortem Human Dura Mater Cells Exhibit Phenotypic, Transcriptomic and Genetic Abnormalities that Impact their Use for Disease Modeling |
title_full_unstemmed | Postmortem Human Dura Mater Cells Exhibit Phenotypic, Transcriptomic and Genetic Abnormalities that Impact their Use for Disease Modeling |
title_short | Postmortem Human Dura Mater Cells Exhibit Phenotypic, Transcriptomic and Genetic Abnormalities that Impact their Use for Disease Modeling |
title_sort | postmortem human dura mater cells exhibit phenotypic, transcriptomic and genetic abnormalities that impact their use for disease modeling |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9622518/ https://www.ncbi.nlm.nih.gov/pubmed/35809166 http://dx.doi.org/10.1007/s12015-022-10416-x |
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