التفاصيل البيبلوغرافية
| العنوان: |
Dual function of PHF16 in reinstating homeostasis of murine intestinal epithelium after crypt regeneration. |
| المؤلفون: |
Ahn, Jun-Yeong1,2 (AUTHOR), Kim, Somi1,3 (AUTHOR), Rok Kim, Chang1,2 (AUTHOR), Lee, Ji-Hyun4 (AUTHOR), Kim, Jong Min1,2 (AUTHOR), Klompstra, Thomas M.4 (AUTHOR), Ha Choi, Yoon3 (AUTHOR), Jeon, Yoon5 (AUTHOR), Na, Yongwoo2 (AUTHOR), Kim, Jong-Seo2,6 (AUTHOR), Okada, Yuki7 (AUTHOR), Lee, Ho5 (AUTHOR), Kim, Ik Soo1,8 (AUTHOR) iksookim@gachon.ac.kr, Kim, Jong Kyoung1,3,9 (AUTHOR) blkimjk@postech.ac.kr, Koo, Bon-Kyoung1,3,4 (AUTHOR) koobk@ibs.re.kr, Baek, Sung Hee1,2 (AUTHOR) sbaek@snu.ac.kr |
| المصدر: |
Developmental Cell. Dec2024, Vol. 59 Issue 23, p3089-31310. 28222p. |
| مصطلحات موضوعية: |
*INTESTINAL mucosa, *RETINOIC acid receptors, *UBIQUITIN ligases, *STEM cells, *RNA sequencing |
| مستخلص: |
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. [Display omitted] • PHF16 is required for intestinal regeneration following irradiation • PHF16 is essential for timely exit from the regenerative phase • The PHF16/HBO1 complex promotes the differentiation of revival stem cells • PHF16 functions as an E3 ligase for CDC73 to suppress the expression of fetal genes Ahn and Kim et al. report that PHF16 controls the timely termination of intestinal injury response and the completion of regeneration. PHF16 promotes the expression of differentiation genes through its interaction with the HBO1 complex, while also acting as an E3 ligase for CDC73 to suppress the expression of fetal genes. [ABSTRACT FROM AUTHOR] |
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