RT Journal Article
T1 The impact of transposable element activity on therapeutically relevant human stem cells
A1 Schumann, Gerald G.
A1 Fuchs, Nina V.
A1 Tristán-Ramos, Pablo
A1 Sebe, Attila
A1 Ivics, Zoltán
A1 Heras, Sara R.
K1 Adult stem cells
K1 Genomic destabilization
K1 LINE-1
K1 Methylation
K1 Pluripotent stem cells
K1 Regenerative medicine
K1 Restriction
K1 Transposable elements
K1 Células madre adultas
K1 Genomic instability
K1 Inestabilidad genómica
K1 Metilación
K1 Células madre pluripotentes
K1 Medicina regenerativa
K1 Elementos transponibles de ADN
K1 DNA transposable elements
AB Human stem cells harbor significant potential for basic and clinical translational research as well as regenerative medicine. Currently ~ 3000 adult and ~ 30 pluripotent stem cell-based, interventional clinical trials are ongoing worldwide, and numbers are increasing continuously. Although stem cells are promising cell sources to treat a wide range of human diseases, there are also concerns regarding potential risks associated with their clinical use, including genomic instability and tumorigenesis concerns. Thus, a deeper understanding of the factors and molecular mechanisms contributing to stem cell genome stability are a prerequisite to harnessing their therapeutic potential for degenerative diseases. Chemical and physical factors are known to influence the stability of stem cell genomes, together with random mutations and Copy Number Variants (CNVs) that accumulated in cultured human stem cells. Here we review the activity of endogenous transposable elements (TEs) in human multipotent and pluripotent stem cells, and the consequences of their mobility for genomic integrity and host gene expression. We describe transcriptional and post-transcriptional mechanisms antagonizing the spread of TEs in the human genome, and highlight those that are more prevalent in multipotent and pluripotent stem cells. Notably, TEs do not only represent a source of mutations/CNVs in genomes, but are also often harnessed as tools to engineer the stem cell genome; thus, we also describe and discuss the most widely applied transposon-based tools and highlight the most relevant areas of their biomedical applications in stem cells. Taken together, this review will contribute to the assessment of the risk that endogenous TE activity and the application of genetically engineered TEs constitute for the biosafety of stem cells to be used for substitutive and regenerative cell therapies.
PB BioMed Central Ltd.
YR 2019
FD 2019-03-09
LK http://hdl.handle.net/10668/3151
UL http://hdl.handle.net/10668/3151
LA en
NO Schumann GG, Fuchs NV, Tristán-Ramos P, Sebe A, Ivics Z, Heras SR. The impact of transposable element activity on therapeutically relevant human stem cells. Mob DNA. 2019 Mar 9;10:9.
DS RISalud
RD Apr 11, 2025