The MicroRNA-371 Family as Plasma Biomarkers for Monitoring Undifferentiated and Potentially Malignant Human Pluripotent Stem Cells in Teratoma Assays
| Autor: | Gemma Perretta, Leendert H. J. Looijenga, Ad J. M. Gillis, J. Wolter Oosterhuis, Lambert C. J. Dorssers, Ton van Agthoven, Daniela C.F. Salvatori, Maria Gomes Fernandes, Hans Stoop, Christine L. Mummery, Jan-Bas Prins |
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| Přispěvatelé: | Pathology |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
embryonal carcinoma
Pluripotent Stem Cells 0301 basic medicine Time Factors Transgene Malignant Germ Cell Tumor Biology Biochemistry Article Cell Line Embryonal carcinoma Mice 03 medical and health sciences microRNA Biomarkers Tumor Genetics medicine Animals Humans human pluripotent stem cells RNA Messenger Induced pluripotent stem cell lcsh:QH301-705.5 malignant elements Principal Component Analysis Messenger RNA lcsh:R5-920 Teratoma Cell Differentiation human germ cell tumors Cell Biology Neoplasms Germ Cell and Embryonal medicine.disease Xenograft Model Antitumor Assays Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology lcsh:Biology (General) Cancer research Biological Assay lcsh:Medicine (General) Reprogramming Developmental Biology |
| Zdroj: | Stem Cell Reports, 11(6), 1493-1505. Cell Press Stem Cell Reports, Vol 11, Iss 6, Pp 1493-1505 (2018) Stem Cell Reports Stem Cell Reports, 11(6), 1493-1505 |
| ISSN: | 2213-6711 |
| Popis: | Summary Predicting developmental potency and risk of posttransplantation tumor formation by human pluripotent stem cells (hPSCs) and their derivatives largely rely on classical histological analysis of teratomas. Here, we investigated whether an assay based on microRNAs (miRNA) in blood plasma is able to detect potentially malignant elements. Several hPSCs and human malignant germ cell tumor (hGCT) lines were investigated in vitro and in vivo after mouse xenografting. The multiple conventional hPSC lines generated mature teratomas, while xenografts from induced hPSCs (hiPSCs) with reactivated reprogramming transgenes and hGCT lines contained undifferentiated and potentially malignant components. The presence of these elements was reflected in the mRNA and miRNA profiles of the xenografts with OCT3/4 mRNA and the miR-371 and miR-302 families readily detectable. miR-371 family members were also identified in mouse plasma faithfully reporting undifferentiated elements in the xenografts. This study demonstrated that undifferentiated and potentially malignant cells could be detected in vivo. Highlights • Side-by-side comparison of cells and xenografts/teratomas derived from hPSCs and hGCTs • Xenografts from hPSCs and hGCTs showed the same histogenesis, mRNA and microRNA profile • miR-371 and -302 diagnosed undifferentiated/malignant cells in hPSC-derived xenografts • miR-371 diagnosed undifferentiated/malignant cells in blood of hPSCs injected mice Salvatori et al. showed histological, mRNA, microRNA similarities between human germ cell tumors and xenografts derived from human pluripotent stem cells (hPSCs). miR-371, -302, and C19MC families were present in the blood plasma of mice after injection of hPSCs (teratoma assay) and were indicative of undifferentiated and potentially malignant cells in the growing xenograft. |
| Databáze: | OpenAIRE |
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