Modeling altered T-cell development with induced pluripotent stem cells from patients with RAG1-dependent immune deficiencies

Author:

Brauer Patrick M.1ORCID,Pessach Itai M.23,Clarke Erik4,Rowe Jared H.2,Ott de Bruin Lisa2,Lee Yu Nee2,Dominguez-Brauer Carmen5,Comeau Anne M.6,Awong Geneve17,Felgentreff Kerstin2,Zhang Yuhang H.8,Bredemeyer Andrea9,Al-Herz Waleed10,Du Likun2,Ververs Francesca2,Kennedy Marion7,Giliani Silvia11,Keller Gordon7,Sleckman Barry P.9,Schatz David G.812,Bushman Frederic D.4,Notarangelo Luigi D.213ORCID,Zúñiga-Pflücker Juan Carlos1

Affiliation:

1. Sunnybrook Research Institute, and Department of Immunology, University of Toronto, Toronto, ON, Canada;

2. Division of Immunology, Boston Children’s Hospital, Boston, MA;

3. Department of Pediatric Critical Care, Sheba Medical Center, Tel-Aviv University, Tel-Aviv, Israel;

4. Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;

5. Ontario Cancer Institute, University Health Network, Toronto, ON, Canada;

6. Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA;

7. McEwen Centre for Regenerative Medicine, University Health Network, Toronto, ON, Canada;

8. Departments of Immunobiology and Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, CT;

9. Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO;

10. Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait;

11. “Angelo Nocivelli” Institute for Molecular Medicine, University of Brescia, Brescia, Italy;

12. Howard Hughes Medical Institute, New Haven, CT; and

13. Harvard Stem Cell Institute, Harvard University, Cambridge, MA

Abstract

Key Points Upon in vitro differentiation, iPSCs obtained from patients with SCID and OS show a similar block in T-cell development. Presence of unresolved single-strand DNA breaks in developing T cells from OS patient-derived iPSCs affects their differentiation.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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