Postmortem Human Dura Mater Cells Exhibit Phenotypic, Transcriptomic and Genetic Abnormalities that Impact their Use for Disease Modeling
(2022) In Stem Cell Reviews and Reports 18(8). p.3050-3065- Abstract
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... (More)
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.
(Less)
- author
- publishing date
- 2022-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Humans, Animals, Mice, Transcriptome, Dura Mater/metabolism, Cell Differentiation/genetics, Fibroblasts, Cells, Cultured
- in
- Stem Cell Reviews and Reports
- volume
- 18
- issue
- 8
- pages
- 16 pages
- publisher
- Springer
- external identifiers
-
- scopus:85133687925
- pmid:35809166
- ISSN
- 2629-3269
- DOI
- 10.1007/s12015-022-10416-x
- language
- English
- LU publication?
- no
- additional info
- © 2022. The Author(s).
- id
- 1ab0c3a0-5e5a-4adb-b4a6-79ec874ad919
- date added to LUP
- 2022-12-21 14:58:26
- date last changed
- 2024-04-18 14:24:45
@article{1ab0c3a0-5e5a-4adb-b4a6-79ec874ad919,
abstract = {{<p>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.</p>}},
author = {{Argouarch, Andrea R and Schultz, Nina and Yang, Andrew C and Jang, Yeongjun and Garcia, Kristle and Cosme, Celica G and Corrales, Christian I and Nana, Alissa L and Karydas, Anna M and Spina, Salvatore and Grinberg, Lea T and Miller, Bruce and Wyss-Coray, Tony and Abyzov, Alexej and Goodarzi, Hani and Seeley, William W and Kao, Aimee W}},
issn = {{2629-3269}},
keywords = {{Humans; Animals; Mice; Transcriptome; Dura Mater/metabolism; Cell Differentiation/genetics; Fibroblasts; Cells, Cultured}},
language = {{eng}},
number = {{8}},
pages = {{3050--3065}},
publisher = {{Springer}},
series = {{Stem Cell Reviews and Reports}},
title = {{Postmortem Human Dura Mater Cells Exhibit Phenotypic, Transcriptomic and Genetic Abnormalities that Impact their Use for Disease Modeling}},
url = {{http://dx.doi.org/10.1007/s12015-022-10416-x}},
doi = {{10.1007/s12015-022-10416-x}},
volume = {{18}},
year = {{2022}},
}