A Comprehensive, Ethnically Diverse Library of Sickle Cell Disease-Specific Induced Pluripotent Stem Cells
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
BU1 iPSC has been extensively characterized and used in the lab at the CReM.
“We chose BU1 iPSC as our targeting clone, which has been extensively characterized and used in our lab at the CReM [21].”
From Modeling APC mutagenesis and familial adenomatous polyposis using human iPS cells (2018) · cites this paper as [21]
The Results section on genetic characterization describes the paper’s banked sickle-cell iPSC lines, and Experimental Procedures describes how the library was generated. Neither identifies BU1 or establishes that it was extensively characterized and used at the CReM; searches for BU1, BU-1, and CReM did not find a passage addressing that claim. (LLM, conf=0.73)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Induced Pluripotent Stem Cell Generation Using a Single Lentiviral Stem Cell Cassette
Sommer, C. A., Stadtfeld, M., Murphy, G. J., Hochedlinger, K., Kotton, D. N., & Mostoslavsky, G. (2009) · Stem Cells · doi:10.1634/stemcells.2008-1075 · Cited by 676 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 17
- Alsultan A. Ngo D.A. Farrell J.J. Akinsheye I. Solovieff N. Ghabbour H.A. Al-Ali A. Alsuliman A. Al-Baghshi M. Albu-Ali W. A functional promoter polymorphism of the delta-globin gene is a specific marker of the Arab-Indian haplotype Am. J. Hematol. 87 2012 824 826 22641479
- Cacchiarelli D. Trapnell C. Ziller M.J. Soumillon M. Cesana M. Karnik R. Donaghey J. Smith Z.D. Ratanasirintrawoot S. Zhang X. Integrative analyses of human reprogramming reveal dynamic nature of induced pluripotency Cell 162 2015 412 424 26186193 PMC4511597
- Cradick T.J. Fine E.J. Antico C.J. Bao G. CRISPR/Cas9 systems targeting beta-globin and CCR5 genes have substantial off-target activity Nucleic Acids Res. 41 2013 9584 9592 23939622 PMC3814385
- Ding Q. Regan S.N. Xia Y. Oostrom L.A. Cowan C.A. Musunuru K. Enhanced efficiency of human pluripotent stem cell genome editing through replacing TALENs with CRISPRs Cell Stem Cell 12 2013 393 394 23561441 PMC3925309
- Heigwer F. Kerr G. Boutros M. E-CRISP: fast CRISPR target site identification Nat. Methods 11 2014 122 123 24481216
- Huang X. Wang Y. Yan W. Smith C. Ye Z. Wang J. Gao Y. Mendelsohn L. Cheng L. Production of gene-corrected adult beta globin protein in human erythrocytes differentiated from patient iPSCs after genome editing of the sickle point mutation Stem Cells 33 2015 1470 1479 25702619 PMC4628786
- Kauf T.L. Coates T.D. Huazhi L. Mody-Patel N. Hartzema A.G. The cost of health care for children and adults with sickle cell disease Am. J. Hematol. 84 2009 323 327 19358302
- Kola I. Landis J. Can the pharmaceutical industry reduce attrition rates? Nat. Rev. Drug Discov. 3 2004 711 715 15286737
- Little S. Amplification-refractory mutation system (ARMS) analysis of point mutations Curr. Protoc. Hum. Genet Chapter 9 2001 Unit 9.8 18428319
- Montague T.G. Cruz J.M. Gagnon J.A. Church G.M. Valen E. CHOPCHOP: a CRISPR/Cas9 and TALEN web tool for genome editing Nucleic Acids Res. 42 Web Server issue 2014 W401 W407 24861617 PMC4086086
- Ngo D.A. Aygun B. Akinsheye I. Hankins J.S. Bhan I. Luo H.Y. Steinberg M.H. Chui D.H. Fetal haemoglobin levels and haematological characteristics of compound heterozygotes for haemoglobin S and deletional hereditary persistence of fetal haemoglobin Br. J. Haematol. 156 2012 259 264 22017641 PMC6605093
- Piel F.B. Hay S.I. Gupta S. Weatherall D.J. Williams T.N. Global burden of sickle cell anaemia in children under five, 2010-2050: modelling based on demographics, excess mortality, and interventions PLoS Med. 10 2013 e1001484 23874164 PMC3712914
- Piel F.B. Patil A.P. Howes R.E. Nyangiri O.A. Gething P.W. Dewi M. Temperley W.H. Williams T.N. Weatherall D.J. Hay S.I. Global epidemiology of sickle haemoglobin in neonates: a contemporary geostatistical model-based map and population estimates Lancet 381 2013 142 151 23103089 PMC3547249
- Smith B.W. Rozelle S.S. Leung A. Ubellacker J. Parks A. Nah S.K. French D. Gadue P. Monti S. Chui D.H. The aryl hydrocarbon receptor directs hematopoietic progenitor cell expansion and differentiation Blood 122 2013 376 385 23723449 PMC3716202
- Somers A. Jean J.C. Sommer C.A. Omari A. Ford C.C. Mills J.A. Ying L. Sommer A.G. Jean J.M. Smith B.W. Generation of transgene-free lung disease-specific human induced pluripotent stem cells using a single excisable lentiviral stem cell cassette Stem Cells 28 2010 1728 1740 20715179 PMC3422663
- Sommer A.G. Rozelle S.S. Sullivan S. Mills J.A. Park S.M. Smith B.W. Iyer A.M. French D.L. Kotton D.N. Gadue P. Generation of human induced pluripotent stem cells from peripheral blood using the STEMCCA lentiviral vector J. Vis. Exp. 2012 PMC3499070 23149977
- Steinberg M.H. Forget B.G. Higgs D.R. Weatherall D.J. Disorders of Hemoglobin: Genetics, Pathophysiology, Clinical Management 2009 Cambridge University Press
Cited by
Sorted by citations
Modeling APC mutagenesis and familial adenomatous polyposis using human iPS cells
Sommer, C. A., Capilla, A., Molina-Estevez, F. J., Gianotti-Sommer, A., Skvir, N., Caballero, I., Chowdhury, S., & Mostoslavsky, G. (2018) · PLOS ONE · doi:10.1371/journal.pone.0200657 · Cited by 39 · see citing works
“We chose BU1 iPSC as our targeting clone, which has been extensively characterized and used in our lab at the CReM [21].”
MethodInfluentialSelf-citationSchaniel, C., Dhanan, P., Hu, B., Xiong, Y., Raghunandan, T., Gonzalez, D. M., Dariolli, R., D'Souza, S. L., Yadaw, A. S., Hansen, J., et al. (2021) · Stem Cell Reports · doi:10.1016/j.stemcr.2021.10.005 · Cited by 26 · see citing works
Vathipadiekal, V., Farrell, J. J., Wang, S., Edward, H. L., Shappell, H., Al‐Rubaish, A. M., Al‐Muhanna, F., Naserullah, Z., Alsuliman, A., Qutub, H. O., et al. (2016) · American Journal of Hematology · doi:10.1002/ajh.24527 · Cited by 20 · see citing works
Self-citation
- Authors
- Park, S., Gianotti-Sommer, A., Molina-Estevez, F. J., Vanuytsel, K., Skvir, N., Leung, A., Rozelle, S. S., Shaikho, E. M., Weir, I., Jiang, Z., Luo, H.-Y., Chui, D. H. K., Figueiredo, M. S., Alsultan, A., Al-Ali, A., Sebastiani, P., Steinberg, M. H., Mostoslavsky, G., & Murphy, G. J.
- Affiliations
- Boston University (US)
- Boston Medical Center (US)
- King Saud University (SA)
- Corresponding author
- Mostoslavsky, Gustavo
- Murphy, George J.
- ORCID
- Venue
- Stem Cell Reports
- Publisher
- Elsevier BV
- Published
- 2017-04
- Volume
- 8
- Issue
- 4
- Pages
- 1076-1085
- ISSN
- 2213-6711 (ISSN-L)
- PMC
- PMC5390092
- OpenAlex
- W2572921361
- Cited by
- 50
- References
- 1
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 1 · 2022: 7 · 2021: 9 · 2020: 7 · 2019: 6 · 2018: 6 · 2017: 4 · 2016: 1
- FWCI
- 3.61
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UNIFESP Institutional Repository (Universidade Federal de São Paulo) (submittedVersion)
- Funders
- NIH/NHLBI (U01HL107443)
- University of Dammam (SP 11/2011)
- Office of Collaboration and Knowledge Exchange
- Training grant for Biostatistics (5T32GM074905)
- Training Grant for Hematology (5T32 HL007501)
- Topics
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- sickle cell disease, induced pluripotent stem cells, ethnic diversity, beta-globin gene haplotypes, fetal hemoglobin, disease severity, CRISPR gene editing
- MeSH terms
- Adolescent, Adult, Anemia, Sickle Cell, Base Sequence, Cell Line, Cells, Cultured, Child, Child, Preschool, Female, Fetal Hemoglobin, Haplotypes, Hemoglobin, Sickle, Humans, Male, Middle Aged, Polymorphism, Genetic, Genetic Therapy, Point Mutation, Erythroid Cells, beta-Globins, Young Adult, Induced Pluripotent Stem Cells, Transcriptome, CRISPR-Cas Systems
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
