Wedelolactone Enhances Odontoblast Differentiation by Promoting Wnt/-Catenin Signaling Pathway and Suppressing NF-B Signaling Pathway
CELLULAR REPROGRAMMING
Authors: Wang, Chenfei; Song, Yihua; Gu, Zhifeng; Lian, Min; Huang, Dan; Lu, Xiaohui; Feng, Xingmei; Lu, Qi
Abstract
Wedelolactone is a multitarget natural plant compound with many pharmacological activities, including anti-inflammatory, anticancer, and antiosteoporosis. In this study, dental pulp stem cells (DPSCs) were treated with or without wedelolactone. We found that wedelolactone stimulated odontoblast differentiation and mineralization. At the molecular level, wedelolactone directly promoted the nuclear accumulation of -catenin, and thereafter stimulated the expression of odontoblast-related marker genes containing dentin matrix protein-1 (DMP1), dentin sialophosphoprotein (DSPP), and runt-related transcription factor 2 (Runx2). Furthermore, wedelolactone upregulated the expression of IB and inhibited phosphonation and nuclear migration of p65. As a result, wedelolactone remarkably induced odontoblast differentiation through semaphorin 3A (Sema3A)/neuropilin-1 (NRP1) pathway-mediated -catenin activation and nuclear factor kappa B (NF-B) pathway inhibition. Our findings provide novel perceptions on odontogenic differentiation of DPSCs.
Critical role for TRIM28 and HP1 beta/gamma in the epigenetic control of T cell metabolic reprograming and effector differentiation
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Authors: Gehrmann, Ulf; Burbage, Marianne; Zueva, Elina; Goudot, Christel; Esnault, Cyril; Ye, Mengliang; Carpier, Jean-Marie; Burgdorf, Nina; Hoyler, Thomas; Suarez, Guadalupe; Joannas, Leonel; Heurtebise-Chretien, Sandrine; Durand, Sylvere; Panes, Rebecca; Bellemare-Pelletier, Angelique; Saez, Pablo J.; Aprahamian, Fanny; Lefevre, Deborah; Adoue, Veronique; El Aabidine, Amal Zine; Ahmad, Maqbool Muhammad; Hivroz, Claire; Joffre, Olivier; Cammas, Florence; Kroemer, Guido; Gagnon, Etienne; Andrau, Jean-Christophe; Amigorena, Sebastian
Abstract
Naive CD4(+) T lymphocytes differentiate into different effector types, including helper and regulatory cells (Th and Treg, respectively). Heritable gene expression programs that define these effector types are established during differentiation, but little is known about the epigenetic mechanisms that install and maintain these programs. Here, we use mice defective for different components of heterochromatin-dependent gene silencing to investigate the epigenetic control of CD4+ T cell plasticity. We show that, upon T cell receptor (TCR) engagement, naive and regulatory T cells defective for TRIM28 (an epigenetic adaptor for histone binding modules) or for heterochromatin protein 1 beta and. isoforms (HP1 beta/gamma, 2 histone-binding factors involved in gene silencing) fail to effectively signal through the PI3K-AKT-mTOR axis and switch to glycolysis. While differentiation of naive TRIM28(-/-) T cells into cytokine-producing effector T cells is impaired, resulting in reduced induction of autoimmune colitis, TRIM28(-/-) regulatory T cells also fail to expand in vivo and to suppress autoimmunity effectively. Using a combination of transcriptome and chromatin immunoprecipitation-sequencing (ChIP-seq) analyses for H3K9me3, H3K9Ac, and RNA polymerase II, we show that reduced effector differentiation correlates with impaired transcriptional silencing at distal regulatory regions of a defined set of Treg-associated genes, including, for example, NRP1 or Snai3. We conclude that TRIM28 and HP1 beta/gamma control metabolic reprograming through epigenetic silencing of a defined set of Treg-characteristic genes, thus allowing effective T cell expansion and differentiation into helper and regulatory phenotypes.
COA
