Discordance between chromatin accessibility and transcriptional activity during the human primed-to-naïve pluripotency transition process

Zhifen Tu; Yan Bi; Tengyan Mao; Hong Wang; Shaorong Gao; Yixuan Wang

doi:10.1186/s13619-023-00179-2

Discordance between chromatin accessibility and transcriptional activity during the human primed-to-naïve pluripotency transition process

Cell Regen. 2023 Nov 8;12(1):35. doi: 10.1186/s13619-023-00179-2.

Authors

Zhifen Tu^#^{1

2}, Yan Bi^#^{2

3}, Tengyan Mao^#^{1

2}, Hong Wang^{1

2

3}, Shaorong Gao^{4

5

6}, Yixuan Wang^{7

8}

Affiliations

¹ Translational Medical Center for Stem Cell Therapy & Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200120, China.
² Frontier Science Center for Stem Cell Research, Tongji University, 1239 Siping Road, Shanghai, 200092, China.
³ Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
⁴ Translational Medical Center for Stem Cell Therapy & Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200120, China. gaoshaorong@tongji.edu.cn.
⁵ Frontier Science Center for Stem Cell Research, Tongji University, 1239 Siping Road, Shanghai, 200092, China. gaoshaorong@tongji.edu.cn.
⁶ Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China. gaoshaorong@tongji.edu.cn.
⁷ Translational Medical Center for Stem Cell Therapy & Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200120, China. wangyixuan@tongji.edu.cn.
⁸ Frontier Science Center for Stem Cell Research, Tongji University, 1239 Siping Road, Shanghai, 200092, China. wangyixuan@tongji.edu.cn.

^# Contributed equally.

Abstract

Naïve pluripotent state can be obtained by several strategies from various types of cells, in which the cell fate roadmap as well as key biological events involved in the journey have been described in detail. Here, we carefully explored the chromatin accessibility dynamics during the primed-to-naïve transition by adopting a dual fluorescent reporter system and the assay for transposase-accessible chromatin (ATAC)-seq. Our results revealed critical chromatin remodeling events and highlight the discordance between chromatin accessibility and transcriptional activity. We further demonstrate that the differential epigenetic modifications and transcription factor (TF) activities may play a critical role in regulating gene expression, and account for the observed variations in gene expression despite similar chromatin landscapes.

Keywords: Discordance between chromatin accessibility and transcriptional activity; Dual reporter system; Histone modifications; Naïve pluripotency; Primed-to-naïve transition.

Grants and funding

31721003/National Natural Science Foundation of China