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Chromatin Dynamics in Intestinal Epithelial Homeostasis: A Paradigm of Cell Fate Determination versus Cell Plasticity
Stem Cell Reviews and Reports ( IF 4.8 ) Pub Date : 2020-10-13 , DOI: 10.1007/s12015-020-10055-0
Jérémie Rispal 1 , Fabrice Escaffit 1 , Didier Trouche 1
Affiliation  

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.



中文翻译:

肠道上皮稳态中的染色质动力学:细胞命运决定与细胞可塑性的范式

肠上皮的快速更新是由位于隐窝底部的干细胞池介导的,产生高度增殖的祖细胞,这些祖细胞反过来在沿绒毛迁移过程中分化。更新和分化之间的平衡对于组织稳态的建立和维持至关重要,并受信号通路(Wnt、Notch、Bmp...)和特定转录因子(TCF4、CDX2...)的调节。这种调节通过调节细胞转录组来控制肠细胞的身份。最近,染色质修饰和动力学已被确定为连接信号通路和转录调节控制肠道稳态的主要参与者。在这篇综述中,我们综合了涉及控制肠道细胞命运的染色质动力学的许多方面,例如干性维持、祖先身份、谱系选择和承诺以及终末分化。此外,我们展示了染色质动力学在肠细胞可塑性中的基本作用的最新数据。事实上,这种可塑性,包括去分化过程或对环境线索(如微生物群的存在或食物摄入)的反应,是器官生理学的核心。最后,我们讨论了染色质动力学在上述机制缺陷引起的疾病的出现和治疗中的作用,如胃肠癌、炎症性肠病或肠易激综合征。我们展示了染色质动力学在肠细胞可塑性中的基本作用的最新数据。事实上,这种可塑性,包括去分化过程或对环境线索(如微生物群的存在或食物摄入)的反应,是器官生理学的核心。最后,我们讨论了染色质动力学在上述机制缺陷引起的疾病的出现和治疗中的作用,如胃肠癌、炎症性肠病或肠易激综合征。我们展示了染色质动力学在肠细胞可塑性中的基本作用的最新数据。事实上,这种可塑性,包括去分化过程或对环境线索(如微生物群的存在或食物摄入)的反应,是器官生理学的核心。最后,我们讨论了染色质动力学在由上述机制缺陷引起的疾病的出现和治疗中的作用,如胃肠癌、炎症性肠病或肠易激综合征。

更新日期:2020-10-13
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