| Literature DB >> 29625068 |
Shangtao Cao1, Shengyong Yu2, Dongwei Li2, Jing Ye2, Xuejie Yang1, Chen Li1, Xiaoshan Wang3, Yuanbang Mai2, Yue Qin1, Jian Wu1, Jiangping He1, Chunhua Zhou1, He Liu1, Bentian Zhao2, Xiaodong Shu4, Chuman Wu2, Ruiping Chen5, Waiyee Chan6, Guangjin Pan4, Jiekai Chen7, Jing Liu8, Duanqing Pei9.
Abstract
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.Entities:
Keywords: AP1; bromodeoxyuridine; cell fate decision; chromatin accessibility; reprogramming; small molecules
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Year: 2018 PMID： 29625068 DOI： 10.1016/j.stem.2018.03.005
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 24.633