BACKGROUND: The novel ability to epigenetically reprogram somatic cells into induced pluripotent stem cells (iPSCs) through the exogenous expression of transcription promises to revolutionize the study of human diseases. OBJECTIVE: Here we report on the generation of 25 iPSC lines from 6 patients with various forms of primary immunodeficiencies (PIDs) affecting adaptive immunity, innate immunity, or both. METHODS: Patients' dermal fibroblasts were reprogrammed by expression of 4 transcription factors, octamer-binding transcription factor 4 (OCT4), sex determining region Y-box 2 (SOX2), Krueppel-like factor 4 (KLF4), and cellular myelomonocytosis proto-oncogene (cMYC), by using a single excisable polycistronic lentiviral vector. RESULTS: iPSCs derived from patients with PIDs show a stemness profile that is comparable with that observed in human embryonic stem cells. After in vitro differentiation into embryoid bodies, pluripotency of the patient-derived iPSC lines was demonstrated by expression of genes characteristic of each of the 3 embryonic layers. We have confirmed the patient-specific origin of the iPSC lines and ascertained maintenance of karyotypic integrity. CONCLUSION: By providing a limitless source of diseased stem cells that can be differentiated into various cell types in vitro, the repository of iPSC lines from patients with PIDs represents a unique resource to investigate the pathophysiology of hematopoietic and extrahematopoietic manifestations of these diseases and might assist in the development of novel therapeutic approaches based on gene correction.
BACKGROUND: The novel ability to epigenetically reprogram somatic cells into induced pluripotent stem cells (iPSCs) through the exogenous expression of transcription promises to revolutionize the study of human diseases. OBJECTIVE: Here we report on the generation of 25 iPSC lines from 6 patients with various forms of primary immunodeficiencies (PIDs) affecting adaptive immunity, innate immunity, or both. METHODS:Patients' dermal fibroblasts were reprogrammed by expression of 4 transcription factors, octamer-binding transcription factor 4 (OCT4), sex determining region Y-box 2 (SOX2), Krueppel-like factor 4 (KLF4), and cellular myelomonocytosis proto-oncogene (cMYC), by using a single excisable polycistronic lentiviral vector. RESULTS: iPSCs derived from patients with PIDs show a stemness profile that is comparable with that observed in human embryonic stem cells. After in vitro differentiation into embryoid bodies, pluripotency of the patient-derived iPSC lines was demonstrated by expression of genes characteristic of each of the 3 embryonic layers. We have confirmed the patient-specific origin of the iPSC lines and ascertained maintenance of karyotypic integrity. CONCLUSION: By providing a limitless source of diseased stem cells that can be differentiated into various cell types in vitro, the repository of iPSC lines from patients with PIDs represents a unique resource to investigate the pathophysiology of hematopoietic and extrahematopoietic manifestations of these diseases and might assist in the development of novel therapeutic approaches based on gene correction.
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Authors: Patrick M Brauer; Itai M Pessach; Erik Clarke; Jared H Rowe; Lisa Ott de Bruin; Yu Nee Lee; Carmen Dominguez-Brauer; Anne M Comeau; Geneve Awong; Kerstin Felgentreff; Yuhang H Zhang; Andrea Bredemeyer; Waleed Al-Herz; Likun Du; Francesca Ververs; Marion Kennedy; Silvia Giliani; Gordon Keller; Barry P Sleckman; David G Schatz; Frederic D Bushman; Luigi D Notarangelo; Juan Carlos Zúñiga-Pflücker Journal: Blood Date: 2016-06-14 Impact factor: 22.113
Authors: Katja G Weinacht; Patrick M Brauer; Kerstin Felgentreff; Alex Devine; Andrew R Gennery; Silvia Giliani; Waleed Al-Herz; Axel Schambach; Juan Carlos Zúñiga-Pflücker; Luigi D Notarangelo Journal: Curr Opin Immunol Date: 2012-07-25 Impact factor: 7.486
Authors: Kerstin Felgentreff; Likun Du; Katja G Weinacht; Kerry Dobbs; Margarita Bartish; Silvia Giliani; Thorsten Schlaeger; Alexander DeVine; Axel Schambach; Lisa J Woodbine; Graham Davies; Sachin N Baxi; Mirjam van der Burg; Jack Bleesing; Andrew Gennery; John Manis; Qiang Pan-Hammarström; Luigi D Notarangelo Journal: Proc Natl Acad Sci U S A Date: 2014-06-02 Impact factor: 11.205