ArticlePloS one2012
Lentiviral transduction of CD34(+) cells induces genome-wide epigenetic modifications.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Development of Stable CHO-K1 Cell Lines Overexpressing Full-Length Human CD20 Antigen.Iranian biomedical journal · 2023Article
- Unraveling the functional role of DNA demethylation at specific promoters by targeted steric blockage of DNA methyltransferase with CRISPR/dCas9.Nature communications · 2021Article
- The Clonal Fate of Live Cells.Molecular therapy. Methods & clinical development · 2017Review
- Engineering cell-based therapies to interface robustly with host physiology.Advanced drug delivery reviews · 2016Review
- Article
- From Genetics to Epigenetics: New Perspectives in Tourette Syndrome Research.Frontiers in neuroscience · 2016Review
- Systemic epigenetic response to recombinant lentiviral vectors independent of proviral integration.Epigenetics & chromatin · 2016Article
- PRC2 inhibition counteracts the culture-associated loss of engraftment potential of human cord blood-derived hematopoietic stem and progenitor cells.Scientific reports · 2015Article
- Periostin secreted by mesenchymal stem cells supports tendon formation in an ectopic mouse model.Stem cells and development · 2014Article
- Hematopoietic stem and progenitor cells acquire distinct DNA-hypermethylation during in vitro culture.Scientific reports · 2013Article
- Comparison of transduction efficiency among various lentiviruses containing GFP reporter in bone marrow hematopoietic stem cell transplantation.Experimental hematology · 2013Article
- SIRT1 is a Highly Networked Protein That Mediates the Adaptation to Chronic Physiological Stress.Genes & cancer · 2013Article
- Biosafety features of lentiviral vectors.Human gene therapy · 2013Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epigenetic modifications may occur during in vitro manipulations of stem cells but these effects have remained unexplored in the context of cell and gene therapy protocols. In an experimental model of ex vivo gene modification for hematopoietic gene therapy, human CD34(+) cells were cultured shortly in the presence of cytokines then with a gene transfer lentiviral vector (LV) expected to transduce cells but to have otherwise limited biological effects on the cells. At the end of the culture, the population of cells remained largely similar at the phenotypic level but some epigenetic changes were evident. Exposure of CD34(+) cells to cytokines increased nuclear expression of epigenetic regulators SIRT1 or DNMT1 and caused genome-wide DNA methylation changes. Surprisingly, the LV caused additional and distinct effects. Large-scale genomic DNA methylation analysis showed that balanced methylation changes occurred in about 200 genes following culture of CD34(+) cells in the presence of cytokines but 900 genes were modified following addition of the LV, predominantly increasing CpG methylation. Epigenetic effects resulting from ex vivo culture and from the use of LV may constitute previously unsuspected sources of biological effects in stem cells and may provide new biomarkers to rationally optimize gene and cell therapy protocols.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.