Despite its exciting potential, chemical induction of pluripotency (CIP) efficiency remains low and the mechanisms are poorly understood. We report the development of an efficient two-step serum- and replating-free CIP protocol and the associated chromatin accessibility dynamics (CAD) by assay for transposase-accessible chromatin (ATAC)-seq. CIP reorganizes the somatic genome to an intermediate state that is resolved under 2iL condition by re-closing previously opened loci prior to pluripotency acquisition with gradual opening of loci enriched with motifs for the OCT/SOX/KLF families. Bromodeoxyuridine, a critical ingredient of CIP, is responsible for both closing and opening critical loci, at least in part by preventing the opening of loci enriched with motifs for the AP1 family and facilitating the opening of loci enriched with SOX/KLF/GATA motifs. These changes differ markedly from CAD observed during Yamanaka-factor-driven reprogramming. Our study provides insights into small-molecule-based reprogramming mechanisms and reorganization of nuclear architecture associated with cell-fate decisions.

中文翻译：

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化学诱导多能性过程中的染色质可及性动力学。

尽管具有令人兴奋的潜力，但多能性（CIP）效率的化学感应仍然很低，并且对机理的了解还很少。我们报告了有效的两步法无血清和无电镀CIP协议和相关的染色质可及性动力学（CAD）的发展，方法是通过转座酶可及的染色质（ATAC）-seq的测定。CIP将体细胞基因组重组为一种中间状态，该状态通过在多能性获得之前重新封闭先前开放的基因座，并逐步开放富含OCT / SOX / KLF家族基序的基因座，从而在2iL条件下得以解决。溴脱氧尿苷是CIP的关键成分，它负责关闭和打开关键基因座，至少部分地是通过防止富含AP1家族基序的基因座的开放，并促进富含SOX / KLF / GATA基序的基因座的开放。这些变化与在Yamanaka因子驱动的重新编程期间观察到的CAD明显不同。我们的研究为基于小分子的重编程机制以及与细胞命运决定相关的核结构重组提供了见识。