%0 Journal Article %A Makoto Motono %A Keiko Hiraki-Kamon %A Masayoshi Kamon %A Hidenori Kiyosawa %A Yoichi Kondo %A Hidemasa Kato %T An improved pipeline for reprogramming human induced pluripotent stem cells with TET1 %D 2022 %R 10.1101/2022.04.29.489839 %J bioRxiv %P 2022.04.29.489839 %X Despite offering insights into regenerative medicine, induced pluripotent stem cells (iPSCs) exhibit inconsistent differentiation potential, which may negatively impact their downstream applications. Here, we potentiated the reprogramming process of iPSCs by adding ten-eleven translocation 1 (TET1), a DNA demethylase, to a conventional reprogramming cocktail to produce TET1-iPSCs (T-iPSCs). We selected differentiation-elite iPSC clones through testing using a default differentiation procedure that challenged the evolutionarily conserved differentiation propensity toward neuroectoderm formation. By comparing the differentiation efficiencies of 46 in-house-generated iPSC clones, we identified extraembryonic markers that may indicate differentiation defects. Elite T-iPSCs showed an epithelialized morphology and differentiated into midbrain dopaminergic neurons with unprecedented fidelity and efficiency. We propose the T-iPSC production pipeline described here as a de facto standard for obtaining human pluripotent stem cells with enhanced differentiation potential.Competing Interest StatementThe authors have declared no competing interest. %U https://www.biorxiv.org/content/biorxiv/early/2022/06/02/2022.04.29.489839.full.pdf