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Background: Gene editing in human patient-specific iPSCs is critical for regenerative medicine. Results: Nonintegrating ␤-thalassemia iPSCs corrected by TALENs display undetectable off targets and can be differentiated into erythroblasts expressing normal ␤-globin. Conclusion: TALENs can be used for HBB correction efficiently in ␤-thalassemia iPSCs with different types. Significance: Our study extends TALENs for gene correction in patient-specific iPSCs and may have applications in cell therapy.

SummaryNicotinamide, the amide form of vitamin B3, is widely used in disease treatments and stem cell applications. However, nicotinamide's impact often cannot be attributed to its nutritional functions. In a vitamin screen, we find that nicotinamide promotes cell survival and differentiation in human pluripotent stem cells. Nicotinamide inhibits the phosphorylation of myosin light chain, suppresses actomyosin contraction, and leads to improved cell survival after individualization. Further analysis demonstrates that nicotinamide is an inhibitor of multiple kinases, including ROCK and casein kinase 1. We demonstrate that nicotinamide affects human embryonic stem cell pluripotency and differentiation as a selective kinase inhibitor. The findings in this report may help researchers design better strategies to develop nicotinamide-related stem cell applications and disease treatments.

Fatty acid metabolism and its regulation are known to play important roles in bacteria and eukaryotes. By contrast, although certain archaea appear to metabolize fatty acids, the regulation of the underlying pathways in these organisms remains unclear. Here, we show that a TetR-family transcriptional regulator (FadR Sa ) is involved in regulation of fatty acid metabolism in the crenarchaeon Sulfolobus acidocaldarius . Functional and structural analyses show that FadR Sa binds to DNA at semi-palindromic recognition sites in two distinct stoichiometric binding modes depending on the operator sequence. Genome-wide transcriptomic and chromatin immunoprecipitation analyses demonstrate that the protein binds to only four genomic sites, acting as a repressor of a 30-kb gene cluster comprising 23 open reading frames encoding lipases and β-oxidation enzymes. Fatty acyl-CoA molecules cause dissociation of FadR Sa binding by inducing conformational changes in the protein. Our results indicate that, despite its similarity in overall structure to bacterial TetR-family FadR regulators, FadR Sa displays a different acyl-CoA binding mode and a distinct regulatory mechanism.