Gene Correction of iPSCs from a Wiskott-Aldrich Syndrome Patient Normalizes the Lymphoid Developmental and Functional Defects
Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency disease caused by mutations in the gene encoding the WAS protein (WASp). Here, induced pluripotent stem cells (iPSCs) were derived from a WAS patient (WAS-iPSC) and the endogenous chromosomal WAS locus was targeted with a wtWAS-2...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-08-01
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| Series: | Stem Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671116300959 |
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| author | Tamara J. Laskowski Yasmine Van Caeneghem Rasoul Pourebrahim Chao Ma Zhenya Ni Zita Garate Ana M. Crane Xuan Shirley Li Wei Liao Manuel Gonzalez-Garay Jose Carlos Segovia David E. Paschon Edward J. Rebar Michael C. Holmes Dan Kaufman Bart Vandekerckhove Brian R. Davis |
| author_facet | Tamara J. Laskowski Yasmine Van Caeneghem Rasoul Pourebrahim Chao Ma Zhenya Ni Zita Garate Ana M. Crane Xuan Shirley Li Wei Liao Manuel Gonzalez-Garay Jose Carlos Segovia David E. Paschon Edward J. Rebar Michael C. Holmes Dan Kaufman Bart Vandekerckhove Brian R. Davis |
| author_sort | Tamara J. Laskowski |
| collection | DOAJ |
| description | Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency disease caused by mutations in the gene encoding the WAS protein (WASp). Here, induced pluripotent stem cells (iPSCs) were derived from a WAS patient (WAS-iPSC) and the endogenous chromosomal WAS locus was targeted with a wtWAS-2A-eGFP transgene using zinc finger nucleases (ZFNs) to generate corrected WAS-iPSC (cWAS-iPSC). WASp and GFP were first expressed in the earliest CD34+CD43+CD45− hematopoietic precursor cells and later in all hematopoietic lineages examined. Whereas differentiation to non-lymphoid lineages was readily obtained from WAS-iPSCs, in vitro T lymphopoiesis from WAS-iPSC was deficient with few CD4+CD8+ double-positive and mature CD3+ T cells obtained. T cell differentiation was restored for cWAS-iPSCs. Similarly, defects in natural killer cell differentiation and function were restored on targeted correction of the WAS locus. These results demonstrate that the defects exhibited by WAS-iPSC-derived lymphoid cells were fully corrected and suggests the potential therapeutic use of gene-corrected WAS-iPSCs. |
| first_indexed | 2024-12-14T13:17:30Z |
| format | Article |
| id | doaj.art-676abc2202b146eb97e086edfc92f229 |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-14T13:17:30Z |
| publishDate | 2016-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-676abc2202b146eb97e086edfc92f2292022-12-21T23:00:00ZengElsevierStem Cell Reports2213-67112016-08-017213914810.1016/j.stemcr.2016.06.003Gene Correction of iPSCs from a Wiskott-Aldrich Syndrome Patient Normalizes the Lymphoid Developmental and Functional DefectsTamara J. Laskowski0Yasmine Van Caeneghem1Rasoul Pourebrahim2Chao Ma3Zhenya Ni4Zita Garate5Ana M. Crane6Xuan Shirley Li7Wei Liao8Manuel Gonzalez-Garay9Jose Carlos Segovia10David E. Paschon11Edward J. Rebar12Michael C. Holmes13Dan Kaufman14Bart Vandekerckhove15Brian R. Davis16Center for Stem Cell and Regenerative Medicine, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USALaboratory for Experimental Immunology, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent 9000, BelgiumCenter for Stem Cell and Regenerative Medicine, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USADepartment of Medicine and Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USADepartment of Medicine and Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USACenter for Stem Cell and Regenerative Medicine, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USACenter for Stem Cell and Regenerative Medicine, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USACenter for Stem Cell and Regenerative Medicine, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USACenter for Stem Cell and Regenerative Medicine, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USACenter for Molecular Imaging, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USADifferentiation and Cytometry Unit, Hematopoietic Innovative Therapies Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) - Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Madrid 28040, SpainSangamo BioSciences Inc, Richmond, CA 94804, USASangamo BioSciences Inc, Richmond, CA 94804, USASangamo BioSciences Inc, Richmond, CA 94804, USADepartment of Medicine and Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USALaboratory for Experimental Immunology, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent 9000, BelgiumCenter for Stem Cell and Regenerative Medicine, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USAWiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency disease caused by mutations in the gene encoding the WAS protein (WASp). Here, induced pluripotent stem cells (iPSCs) were derived from a WAS patient (WAS-iPSC) and the endogenous chromosomal WAS locus was targeted with a wtWAS-2A-eGFP transgene using zinc finger nucleases (ZFNs) to generate corrected WAS-iPSC (cWAS-iPSC). WASp and GFP were first expressed in the earliest CD34+CD43+CD45− hematopoietic precursor cells and later in all hematopoietic lineages examined. Whereas differentiation to non-lymphoid lineages was readily obtained from WAS-iPSCs, in vitro T lymphopoiesis from WAS-iPSC was deficient with few CD4+CD8+ double-positive and mature CD3+ T cells obtained. T cell differentiation was restored for cWAS-iPSCs. Similarly, defects in natural killer cell differentiation and function were restored on targeted correction of the WAS locus. These results demonstrate that the defects exhibited by WAS-iPSC-derived lymphoid cells were fully corrected and suggests the potential therapeutic use of gene-corrected WAS-iPSCs.http://www.sciencedirect.com/science/article/pii/S2213671116300959induced pluripotent stem cellsgenome editingimmune deficiencyT cells |
| spellingShingle | Tamara J. Laskowski Yasmine Van Caeneghem Rasoul Pourebrahim Chao Ma Zhenya Ni Zita Garate Ana M. Crane Xuan Shirley Li Wei Liao Manuel Gonzalez-Garay Jose Carlos Segovia David E. Paschon Edward J. Rebar Michael C. Holmes Dan Kaufman Bart Vandekerckhove Brian R. Davis Gene Correction of iPSCs from a Wiskott-Aldrich Syndrome Patient Normalizes the Lymphoid Developmental and Functional Defects Stem Cell Reports induced pluripotent stem cells genome editing immune deficiency T cells |
| title | Gene Correction of iPSCs from a Wiskott-Aldrich Syndrome Patient Normalizes the Lymphoid Developmental and Functional Defects |
| title_full | Gene Correction of iPSCs from a Wiskott-Aldrich Syndrome Patient Normalizes the Lymphoid Developmental and Functional Defects |
| title_fullStr | Gene Correction of iPSCs from a Wiskott-Aldrich Syndrome Patient Normalizes the Lymphoid Developmental and Functional Defects |
| title_full_unstemmed | Gene Correction of iPSCs from a Wiskott-Aldrich Syndrome Patient Normalizes the Lymphoid Developmental and Functional Defects |
| title_short | Gene Correction of iPSCs from a Wiskott-Aldrich Syndrome Patient Normalizes the Lymphoid Developmental and Functional Defects |
| title_sort | gene correction of ipscs from a wiskott aldrich syndrome patient normalizes the lymphoid developmental and functional defects |
| topic | induced pluripotent stem cells genome editing immune deficiency T cells |
| url | http://www.sciencedirect.com/science/article/pii/S2213671116300959 |
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