title: A Comprehensive, Ethnically Diverse Library of Sickle Cell Disease-Specific Induced Pluripotent Stem Cells.
abstract: 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, β-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.
authors.affiliation: Department of Medicine, Center for Regenerative Medicine (CReM), Boston University School of Medicine, 670 Albany Street, 2nd Floor, Boston, MA 02118, USA; Section of Gastroenterology, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Seonmi
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Medicine, Center for Regenerative Medicine (CReM), Boston University School of Medicine, 670 Albany Street, 2nd Floor, Boston, MA 02118, USA; Section of Gastroenterology, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Andreia
authors.initials: A
authors.lastname: Gianotti-Sommer
authors.affiliation: Department of Medicine, Center for Regenerative Medicine (CReM), Boston University School of Medicine, 670 Albany Street, 2nd Floor, Boston, MA 02118, USA; Section of Gastroenterology, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Molina-Estevez
authors.affiliation: Department of Medicine, Center for Regenerative Medicine (CReM), Boston University School of Medicine, 670 Albany Street, 2nd Floor, Boston, MA 02118, USA; Section of Hematology-Oncology, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Kim
authors.initials: K
authors.lastname: Vanuytsel
authors.affiliation: Department of Medicine, Center for Regenerative Medicine (CReM), Boston University School of Medicine, 670 Albany Street, 2nd Floor, Boston, MA 02118, USA; Section of Hematology-Oncology, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Nick
authors.initials: N
authors.lastname: Skvir
authors.affiliation: Department of Medicine, Center for Regenerative Medicine (CReM), Boston University School of Medicine, 670 Albany Street, 2nd Floor, Boston, MA 02118, USA; Section of Hematology-Oncology, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Leung
authors.affiliation: Department of Medicine, Center for Regenerative Medicine (CReM), Boston University School of Medicine, 670 Albany Street, 2nd Floor, Boston, MA 02118, USA; Section of Hematology-Oncology, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Rozelle
authors.affiliation: Bioinformatics Program, Boston University, Boston, MA 02215, USA.
authors.forename: Elmutaz Mohammed
authors.initials: EM
authors.lastname: Shaikho
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Weir
authors.affiliation: Hemoglobin Diagnostic Reference Laboratory, Boston Medical Center, Boston, MA 02118, USA.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Hemoglobin Diagnostic Reference Laboratory, Boston Medical Center, Boston, MA 02118, USA.
authors.forename: Hong-Yuan
authors.initials: HY
authors.lastname: Luo
authors.affiliation: Section of Hematology-Oncology, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA; Hemoglobin Diagnostic Reference Laboratory, Boston Medical Center, Boston, MA 02118, USA.
authors.forename: David H K
authors.initials: DHK
authors.lastname: Chui
authors.affiliation: Hematology and Blood Transfusion Division, Escola Paulista de Medicina, São Paulo 04023-062, Brazil.
authors.forename: Maria Stella
authors.initials: MS
authors.lastname: Figueiredo
authors.affiliation: Department of Pediatrics, Sickle Cell Disease Research Center, College of Medicine, King Saud University, Riyadh 12372, Saudi Arabia.
authors.forename: Abdulraham
authors.initials: A
authors.lastname: Alsultan
authors.affiliation: Center for Research & Medical Consultation, University of Dammam, Dammam 34212, Saudi Arabia.
authors.forename: Amein
authors.initials: A
authors.lastname: Al-Ali
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
authors.forename: Paola
authors.initials: P
authors.lastname: Sebastiani
authors.affiliation: Section of Hematology-Oncology, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA; Center of Excellence in Sickle Cell Disease, Boston Medical Center, Boston, MA 02118, USA.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Steinberg
authors.affiliation: Department of Medicine, Center for Regenerative Medicine (CReM), Boston University School of Medicine, 670 Albany Street, 2nd Floor, Boston, MA 02118, USA; Section of Gastroenterology, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address: gmostosl@bu.edu.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Mostoslavsky
authors.affiliation: Department of Medicine, Center for Regenerative Medicine (CReM), Boston University School of Medicine, 670 Albany Street, 2nd Floor, Boston, MA 02118, USA; Section of Hematology-Oncology, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address: gjmurphy@bu.edu.
authors.forename: George J
authors.initials: GJ
authors.lastname: Murphy
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood / Q000208:ethnology / Q000235:genetics* / Q000628:therapy*; D001483:Base Sequence; D064113:CRISPR-Cas Systems; D002460:Cell Line; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D005319:Fetal Hemoglobin / Q000032:analysis; D015316:Genetic Therapy / Q000379:methods; D006239:Haplotypes; D006451:Hemoglobin, Sickle / Q000235:genetics*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011110:Polymorphism, Genetic; D059467:Transcriptome; D055815:Young Adult; D055544:beta-Globins / Q000235:genetics*
chemical_list: D006451:Hemoglobin, Sickle; D055544:beta-Globins; D005319:Fetal Hemoglobin
keywords: directed differentiation; disease modeling; gene correction; iPSCs; induced pluripotent stem cells; sickle cell disease