Postmortem Human Dura Mater Cells Exhibit Phenotypic, Transcriptomic and Genetic Abnormalities that Impact their Use for Disease Modeling
-
Published:2022-07-09
Issue:8
Volume:18
Page:3050-3065
-
ISSN:2629-3269
-
Container-title:Stem Cell Reviews and Reports
-
language:en
-
Short-container-title:Stem Cell Rev and Rep
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.ORCID
Abstract
AbstractPatient-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
Publisher
Springer Science and Business Media LLC
Reference46 articles.
1. Arredondo, C., Cefaliello, C., Dyrda, A., Jury, N., Martinez, P., Díaz, I., et al. (2022). Excessive release of inorganic polyphosphate by ALS/FTD astrocytes causes non-cell-autonomous toxicity to motoneurons. Neuron, 1–15. https://doi.org/10.1016/j.neuron.2022.02.010 2. Kuo, S. H., Tasset, I., Cheng, M. M., Diaz, A., Pan, M. K., Lieberman, O. J., et al. (2022). Mutant glucocerebrosidase impairs α-synuclein degradation by blockade of chaperone-mediated autophagy. Science Advances, 8(6). https://doi.org/10.1126/sciadv.abm6393 3. Aslanger, A. D., Goncu, B., Duzenli, O. F., Yucesan, E., Sengenc, E., & Yesil, G. (2022). Biallelic loss of TRAPPC9 function links vesicle trafficking pathway to autosomal recessive intellectual disability. Journal of Human Genetics, (October 2021), 3–8. https://doi.org/10.1038/s10038-021-01007-8 4. Hung, C. L. K., Maiuri, T., Bowie, L. E., Gotesman, R., Son, S., Falcone, M., et al. (2018). A patient-derived cellular model for Huntington’s disease reveals phenotypes at clinically relevant CAG lengths. Molecular Biology of the Cell, 29(23), 2809–2820. https://doi.org/10.1091/mbc.E18-09-0590 5. D’Souza, G. X., Rose, S. E., Knupp, A., Nicholson, D. A., Keene, C. D., & Young, J. E. (2020). The application of in vitro-derived human neurons in neurodegenerative disease modeling. Journal of Neuroscience Research, (December 2019), 1–17. https://doi.org/10.1002/jnr.24615
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|