한빛사논문
- 조회102
Jun-Yeong Ahn,1,2,10 Somi Kim,3,10 Chang Rok Kim,1,2 Ji-Hyun Lee,4 Jong Min Kim,1,2 Thomas M. Klompstra,4 Yoon Ha Choi,3 Yoon Jeon,5 Yongwoo Na,2 Jong-Seo Kim,2,6 Yuki Okada,7 Ho Lee,5 Ik Soo Kim,8,* Jong Kyoung Kim,3,9,* Bon-Kyoung Koo,3,4,* and Sung Hee Baek 1,2,11,*
1Creative Research Initiatives Center for Epigenetic Code and Diseases, Seoul National University, Seoul 08826, South Korea
2School of Biological Sciences, Seoul National University, Seoul 08826, South Korea
3Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang 37673, South Korea
4Center for Genome Engineering, Institute for Basic Science, 55, Expo-ro, Yuseong-gu, Daejeon 34126, South Korea
5Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, South Korea
6Center for RNA Research, Institute for Basic Science, School of Biological Sciences, Seoul National University, Seoul 08826, South Korea
7Laboratory of Pathology and Development, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo 113-0032, Japan
8Department of Microbiology, Gachon University College of Medicine, Incheon 21999, South Korea
9Institute for Convergence Research and Education in Advanced Technology, Yonsei University, Seoul 03722, South Korea
10These authors contributed equally
11Lead contact
*Corresponding authors: correspondence to Ik Soo Kim,Jong Kyoung Kim, Bon-Kyoung Koo or Sung Hee Baek
Abstract
Intestinal stem cells (ISCs) are highly vulnerable to damage, being in a constant state of proliferation. Reserve stem cells repair the intestinal epithelium following damage-induced ablation of ISCs. Here, we report that the epigenetic regulator plant homology domain (PHD) finger protein 16 (PHF16) restores homeostasis of the intestinal epithelium after initial damage-induced repair. In Phf16−/Y mice, revival stem cells (revSCs) showed defects in exiting the regenerative state, and intestinal crypt regeneration failed even though revSCs were still induced in response to tissue damage, as observed by single-cell RNA sequencing (scRNA-seq). Analysis of Phf16−/Y intestinal organoids by RNA sequencing (RNA-seq) and ATAC sequencing identified that PHF16 restores homeostasis of the intestinal epithelium by inducing retinoic acid receptor (RAR)/retinoic X receptor (RXR) target genes through HBO1-mediated histone H3K14 acetylation, while at the same time counteracting YAP/TAZ activity by ubiquitination of CDC73. Together, our findings demonstrate the importance of timely suppression of regenerative activity by PHF16 for the restoration of gut homeostasis after acute tissue injury.
논문정보
- Research article
- 2024년 09월 (BRIC 등록일 2024-09-04)
- 국내(교신)+국외 연구진
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