Journal
STEM CELLS AND DEVELOPMENT
Volume 24, Issue 9, Pages 1053-1065Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/scd.2014.0347
Keywords
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Funding
- National Natural Science Foundation-Guangdong Joint Fund [U1132005, 31171229]
- Science and Information Technology of Guangzhou Key Project [2011Y1-00038, 201400000004]
- Guangdong Province Higher Education Funding [Yq2013135]
- General Financial Grant from the China Postdoctoral Science Foundation [2013 M531833]
- Doctoral Foundation from The Third Affiliated Hospital of Guangzhou Medical University, China [2012C63]
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The generation of beta-thalassemia (beta-Thal) patient-specific induced pluripotent stem cells (iPSCs), subsequent homologous recombination-based gene correction of disease-causing mutations/deletions in the beta-globin gene (HBB), and their derived hematopoietic stem cell (HSC) transplantation offers an ideal therapeutic solution for treating this disease. However, the hematopoietic differentiation efficiency of gene-corrected beta-Thal iPSCs has not been well evaluated in the previous studies. In this study, we used the latest gene-editing tool, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9), to correct beta-Thal iPSCs; gene-corrected cells exhibit normal karyotypes and full pluripotency as human embryonic stem cells (hESCs) showed no off-targeting effects. Then, we evaluated the differentiation efficiency of the gene-corrected beta-Thal iPSCs. We found that during hematopoietic differentiation, gene-corrected beta-Thal iPSCs showed an increased embryoid body ratio and various hematopoietic progenitor cell percentages. More importantly, the gene-corrected beta-Thal iPSC lines restored HBB expression and reduced reactive oxygen species production compared with the uncorrected group. Our study suggested that hematopoietic differentiation efficiency of beta-Thal iPSCs was greatly improved once corrected by the CRISPR/Cas9 system, and the information gained from our study would greatly promote the clinical application of beta-Thal iPSC-derived HSCs in transplantation.
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