RNA-sequencing of cells derived from dermis and postmortem dura mater from the same subject

Patient-derived cells hold great promise for precision medicine approaches in human health. Fibroblast cells have been a major source of human cells for reprogramming and differentiating into specific cell types for disease modeling. Such cells can be isolated at various stages during life (presymptomatic, symptomatic, and advanced disease) and thus can potentially be used to model different phases of disease progression. In certain circumstances, however, tissues are not collected during life and only postmortem tissues are the only available source of fibroblasts. Fibroblasts cultured from postmortem human dura mater of individuals with neurodegenerative diseases have been suggested as a primary source of cells 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 requires further characterization. In this study, cells derived from dermal biopsies of living subjects were compared to cells derived from postmortem dura mater. In two instances, we have isolated and compared dermal and dural cell lines from the same subject. Notably, such striking differences were observed between cells of dermal and dural origin that their fibroblast nature was brought into question. 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 dural-derived cells from the same subject were compared, they exhibited significant differences in gene expression profiles. Ultimately, dura mater-derived cells were found to originate from a mixed mural lineage consisting of smooth muscle cells and pericytes. Our study argues for rigorous karyotyping of all postmortem derived cell lines and highlights significant limitations of postmortem human dura mater-derived cells for modeling normal biology or disease-associated pathobiology. Examination of a dura mater-derived cell line compared to dermis fibroblasts from the same subject. Four technical replicates for each line.