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Title: Derivation of healthy hepatocyte-like cells from a female patient with ornithine transcarbamylase deficiency through X-inactivation selection
Authors: Santamaria, Ramon
Ballester, Maria
Garcia-Llorens, Guillem
Martinez, Francisco
Blazquez, Marina
Ribes-Koninckx, Carmen
Castell, Jose V.
Wuestefeld, Torsten
Bort, Roque
Keywords: Science::Biological sciences
Issue Date: 2022
Source: Santamaria, R., Ballester, M., Garcia-Llorens, G., Martinez, F., Blazquez, M., Ribes-Koninckx, C., Castell, J. V., Wuestefeld, T. & Bort, R. (2022). Derivation of healthy hepatocyte-like cells from a female patient with ornithine transcarbamylase deficiency through X-inactivation selection. Scientific Reports, 12(1), 2308-.
Journal: Scientific Reports
Abstract: Autologous cell replacement therapy for inherited metabolic disorders requires the correction of the underlying genetic mutation in patient's cells. An unexplored alternative for females affected from X-linked diseases is the clonal selection of cells randomly silencing the X-chromosome containing the mutant allele, without in vivo or ex vivo genome editing. In this report, we have isolated dermal fibroblasts from a female patient affected of ornithine transcarbamylase deficiency and obtained clones based on inactivation status of either maternally or paternally inherited X chromosome, followed by differentiation to hepatocytes. Hepatocyte-like cells derived from these clones display indistinct features characteristic of hepatocytes, but express either the mutant or wild type OTC allele depending on X-inactivation pattern. When clonally derived hepatocyte-like cells were transplanted into FRG® KO mice, they were able to colonize the liver and recapitulate OTC-dependent phenotype conditioned by X-chromosome inactivation pattern. This approach opens new strategies for cell therapy of X-linked metabolic diseases and experimental in vitro models for drug development for such diseases.
ISSN: 2045-2322
DOI: 10.1038/s41598-022-06184-w
Schools: School of Biological Sciences 
Organisations: Genome Institute of Singapore, A*STAR
National Cancer Centre, Singapore
Rights: © The Author(s) 2022. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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