Chromatin Dynamics in Intestinal Epithelial Homeostasis: A Paradigm of Cell Fate Determination versus Cell Plasticity
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Chromatin Dynamics in Intestinal Epithelial Homeostasis: A Paradigm of Cell Fate Determination versus Cell Plasticity Jérémie Rispal 1 & Fabrice Escaffit 1
&
Didier Trouche 1
Accepted: 5 October 2020 # The Author(s) 2020
Abstract The rapid renewal of intestinal epithelium is mediated by a pool of stem cells, located at the bottom of crypts, giving rise to highly proliferative progenitor cells, which in turn differentiate during their migration along the villus. The equilibrium between renewal and differentiation is critical for establishment and maintenance of tissue homeostasis, and is regulated by signaling pathways (Wnt, Notch, Bmp…) and specific transcription factors (TCF4, CDX2…). Such regulation controls intestinal cell identities by modulating the cellular transcriptome. Recently, chromatin modification and dynamics have been identified as major actors linking signaling pathways and transcriptional regulation in the control of intestinal homeostasis. In this review, we synthesize the many facets of chromatin dynamics involved in controlling intestinal cell fate, such as stemness maintenance, progenitor identity, lineage choice and commitment, and terminal differentiation. In addition, we present recent data underlying the fundamental role of chromatin dynamics in intestinal cell plasticity. Indeed, this plasticity, which includes dedifferentiation processes or the response to environmental cues (like microbiota’s presence or food ingestion), is central for the organ’s physiology. Finally, we discuss the role of chromatin dynamics in the appearance and treatment of diseases caused by deficiencies in the aforementioned mechanisms, such as gastrointestinal cancer, inflammatory bowel disease or irritable bowel syndrome. Keywords Intestinal epithelium . Homeostasis . Stem cell proliferation . Differentiation . Epigenetics . Chromatin remodeler . Histone post-translational modification . Lineage commitment . Response to environment
Introduction The intestinal epithelium is entirely renewed every 3 to 5 days. This renewal is mediated by Intestinal Stem Cells (ISCs), which reside at the bottom of proliferative compartments, called “crypts” [1, 2]. The ISCs divide to self-renew or to give rise to progenitor cells, which in turn undergo several cycles of division before committing to secretory or absorptive lineages [3]. Then, cells migrate along the villi, and acquire terminal differentiation features. When cells reach the top of the Fabrice Escaffit and Didier Trouche contributed equally to this work. * Fabrice Escaffit [email protected] Jérémie Rispal [email protected] Didier Trouche [email protected] 1
LBCMCP, Centre of Integrative Biology (CBI), Université de Toulouse, CNRS, UPS, Toulouse 31062, France
villi, they detach and die by anoikis, a detachment-induced apoptotic process. All these phenotypic shifts are associated with major changes in gene expression [4]. Indeed, about 4000 to 6000 genes are differentially expressed in crypts compared to villus cells [5, 6]. The
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