Targeted genome editing restores T cell differentiation in a humanized X-SCID pluripotent stem cell disease model
Abstract: The generation of T cells from pluripotent stem cells (PSCs) is attractive for investigating T cell development and validating genome editing strategies in vitro. X-linked severe combined immunodeficiency (X-SCID) is an immune disorder caused by mutations in the IL2RG gene and characterised by the absence of T and NK cells in patients. IL2RG encodes the common gamma chain, which is part of several interleukin receptors, including IL-2 and IL-7 receptors. To model X-SCID in vitro, we generated a mouse embryonic stem cell (ESC) line in which a disease-causing human IL2RG gene variant replaces the endogenous Il2rg locus. We developed a stage-specific T cell differentiation protocol to validate genetic correction of the common G691A mutation with transcription activator-like effector nucleases. While all ESC clones could be differentiated to hematopoietic precursor cells, stage-specific analysis of T cell maturation confirmed early arrest of T cell differentiation at the T cell progenitor stage in X-SCID cells. In contrast, genetically corrected ESCs differentiated to CD4 + or CD8 + single-positive T cells, confirming correction of the cellular X-SCID phenotype. This study emphasises the value of PSCs for disease modelling and underlines the significance of in vitro models as tools to validate genome editing strategies before clinical application
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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Scientific reports. - 7 (2017) , 12475, ISSN: 2045-2322
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2019
- Urheber
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Alzuʾbi, Jamal
Pallant, Celeste
Mussolino, Claudio
Howe, Steven J.
Thrasher, Adrian J.
Cathomen, Anton
- DOI
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10.1038/s41598-017-12750-4
- URN
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urn:nbn:de:bsz:25-freidok-1423675
- Rechteinformation
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Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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14.08.2025, 10:56 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Alzuʾbi, Jamal
- Pallant, Celeste
- Mussolino, Claudio
- Howe, Steven J.
- Thrasher, Adrian J.
- Cathomen, Anton
- Universität
Entstanden
- 2019
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