(A) Schematic overview of secondary naïve reprogramming strategy to generate human naïve iPSCs. 1° HEF, primary human embryonic fibroblasts; 1° piPSCs, primary primed iPSCs; 2° hiF, inducible fibroblasts; 2° hiF-T, immortalized inducible fibroblasts; 2° niPSCs, secondary naïve iPSCs. (B) Growth curves of hiF and hiF-T cells at different passages. (C) Alkaline phosphatase (AP) staining representing the naïve reprogramming efficiencies of HEFs, hiFs and hiF-Ts at different passages. (D) Representative images showing the senescent cells in hiFs and hiF-Ts at different passages by senescence-associated-beta-galactosidase (SA-β-GAL) assay. Scale bar, 50 μm. Senescent cells are stained in blue and indicated with red arrowheads.