ArticleStem cell research & therapy2016
Silencing of hepatic fate-conversion factors induce tumorigenesis in reprogrammed hepatic progenitor-like cells.
Article in Stem cell research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- Deciphering Age-Dependent ECM Remodelling in Liver: Proteomic Profiling and Its Implications for Aging and Therapeutic Targets.Cell proliferation · 2025Article
- Transcriptional Control: A Directional Sign at the Crossroads of Adult Hepatic Progenitor Cells' Fates.International journal of biological sciences · 2024Review
- A robust reprogramming strategy for generating hepatocyte-like cells usable in pharmaco-toxicological studies.Stem cell research & therapy · 2023Article
- Modeling a Novel Variant of Glycogenosis IXa Using a Clonal Inducible Reprogramming System to Generate "Diseased" Hepatocytes for Accurate Diagnosis.Journal of personalized medicine · 2022Article
- Derivation of healthy hepatocyte-like cells from a female patient with ornithine transcarbamylase deficiency through X-inactivation selection.Scientific reports · 2022Article
- Direct cell-fate conversion of somatic cells: Toward regenerative medicine and industries.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2020Review
- Glutamine/glutamate metabolism rewiring in reprogrammed human hepatocyte-like cells.Scientific reports · 2019Article
- Direct conversion of human fibroblast to hepatocytes using a single inducible polycistronic vector.Stem cell research & therapy · 2019Article
- Transcription factor induced conversion of human fibroblasts towards the hair cell lineage.PloS one · 2018Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSeveral studies have reported the direct conversion of mouse fibroblasts to hepatocyte-like cells with different degrees of maturation by expression of hepatic fate-conversion factors.
methodsWe have used a combination of lentiviral vectors expressing hepatic fate-conversion factors with Oct4, Sox2, Klf4, and Myc to convert mouse embryonic fibroblasts into hepatic cells.
resultsWe have generated hepatic cells with progenitor-like features (iHepL cells). iHepL cells displayed basic hepatocyte functions but failed to perform functions characteristic of mature hepatocytes such as significant Cyp450 or urea cycle activities. iHepL cells expressed multiple hepatic-specific transcription factors and functional genes characteristic of immature hepatocytes and cholangiocytes, as well as high levels of Foxl1, Cd24a, and Lgr5, specific markers of hepatic progenitor cells. When transplanted into partial hepatectomized and hepatic irradiated mice, they differentiated into hepatocytes and cholangiocytes. However, iHepL cells formed malignant non-teratoma cell aggregations in one out of five engrafted livers and five out of five xenografts assays. All the cells in these tumors had silenced key hepatic fate-conversion factors, and lost hepatic features.
conclusionsThis study highlights the dangers of using pluripotency factors in reprogramming strategies when fate-conversion factors are silenced in vivo, and urges us to perform extensive tumorigenic tests in reprogrammed cells.
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