Artigo
A Comprehensive, Ethnically Diverse Library of Sickle Cell Disease-Specific Induced Pluripotent Stem Cells
Fecha
2017Registro en:
Stem Cell Reports. Cambridge, v. 8, n. 4, p. 1076-1085, 2017.
2213-6711
10.1016/j.stemcr.2016.12.017
WOS:000401129100022
Autor
Park, Seonmi
Gianotti-Sommer, Andreia
Molina-Estevez, Francisco Javier
Vanuytsel, Kim
Skvir, Nick
Leung, Amy
Rozelle, Sarah S.
Shaikho, Elmutaz Mohammed
Weir, Isabelle
Jiang, Zhihua
Luo, Hong-Yuan
Chui, David H. K.
Figueiredo, Maria Stella [UNIFESP]
Alsultan, Abdulraham
Al-Ali, Amein
Sebastiani, Paola
Steinberg, Martin H.
Mostoslavsky, Gustavo
Murphy, George J.
Institución
Resumen
Sickle cell anemia affects millions of people worldwide and is an emerging global health burden. As part of a large NIH-funded NextGen Consortium, we generated a diverse, comprehensive, and fully characterized library of sickle-cell-disease-specific induced pluripotent stem cells (iPSCs) from patients of different ethnicities, beta-globin gene (HBB) haplotypes, and fetal hemoglobin (HbF) levels. iPSCs stand to revolutionize the way we study human development, model disease, and perhaps eventually, treat patients. Here, we describe this unique resource for the study of sickle cell disease, including novel haplotype-specific polymorphisms that affect disease severity, as well as for the development of patient-specific therapeutics for this phenotypically diverse disorder. As a complement to this library, and as proof of principle for future cell-and gene-based therapies, we also designed and employed CRISPR/Cas gene editing tools to correct the sickle hemoglobin (HbS) mutation.