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Open Access Gold möglich sobald Verlagsversion bei der ZB eingereicht worden ist.
Comparative computational analysis to distinguish mesenchymal stem cells from fibroblasts.
Front. Immunol. 14:1270493 (2023)
INTRODUCTION: Mesenchymal stem cells (MSCs) are considered to be the most promising stem cell type for cell-based therapies in regenerative medicine. Based on their potential to home to diseased body sites following a therapeutically application, these cells could (i) differentiate then into organ-specific cell types to locally restore injured cells or, most prominently, (ii) foster tissue regeneration including immune modulations more indirectly by secretion of protective growth factors and cytokines. As tissue-resident stem cells of mesenchymal origin, these cells are morphologically and even molecularly- at least concerning the classical marker genes- indistinguishable from similar lineage cells, particularly fibroblasts. METHODS: Here we used microarray-based gene expression and global DNA methylation analyses as well as accompanying computational tools in order to specify differences between MSCs and fibroblasts, to further unravel potential identity genes and to highlight MSC signaling pathways with regard to their trophic and immunosuppressive action. RESULTS: We identified 1352 differentially expressed genes, of which in the MSCs there is a strong signature for e.g., KRAS signaling, known to play essential role in stemness maintenance, regulation of coagulation and complement being decisive for resolving inflammatory processes, as well as of wound healing particularly important for their regenerative capacity. Genes upregulated in fibroblasts addressed predominately transcription and biosynthetic processes and mapped morphological features of the tissue. Concerning the cellular identity, we specified the already known HOX code for MSCs, established a potential HOX code for fibroblasts, and linked certain HOX genes to functional cell-type-specific properties. Accompanied methylation profiles revealed numerous regions, especially in HOX genes, being differentially methylated, which might provide additional biomarker potential. DISCUSSION: Conclusively, transcriptomic together with epigenetic signatures can be successfully be used for the definition (cellular identity) of MSCs versus fibroblasts as well as for the determination of the superior functional properties of MSCs, such as their immunomodulatory potential.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Adult Stem Cells ; Cellular Identity ; Hox Code ; Inflammation ; Mesenchymal ; Signaling Pathways; In-vitro Generation; Gene-expression; Stromal Cells; Bone-marrow; Promotes; Proliferation; Adventitia; Regulator
ISSN (print) / ISBN
1664-3224
e-ISSN
1664-3224
Zeitschrift
Frontiers in Immunology
Quellenangaben
Band: 14,
Artikelnummer: 1270493
Verlag
Frontiers
Verlagsort
Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Research Unit Radiation Cytogenetics (ZYTO)
CCG Personalized Radiotherapy in Head and Neck Cancer (KKG-KRT)
CCG Personalized Radiotherapy in Head and Neck Cancer (KKG-KRT)
Förderungen
ELAN program of the Medical Faculty, University of Duisburg-Essen
This work was supported by the ELAN program of the Medical Faculty, University of Duisburg-Essen and the Brigitte und Dr. Konstanze Wegener-Stiftung.
This work was supported by the ELAN program of the Medical Faculty, University of Duisburg-Essen and the Brigitte und Dr. Konstanze Wegener-Stiftung.