Genome organiser Satb1 and the control of tissue-specific chromatin remodelling during regeneration of the epidermis

随着组织工程和器官再生方面的重大进展，了解干细胞中的基因表达如何导致它们发展为特殊类型的细胞是很重要的。皮肤上皮是一种自我更新的生物结构，由寄居在基底层的干细胞组成，并分化为基底层以上的角质形成细胞。这一过程导致形成一种表皮屏障，保护有机体免受有害环境因素的影响，并伴随着一些表皮特异基因的激活，这些基因位于基因组中，作为四条不同染色体上的簇。然而，目前还不清楚这些簇是如何分布在表皮细胞的细胞核中的，以及是什么调节了它们的核内排列和活动。我们将测试这一过程是否受到特定的Satb1蛋白的调控，该蛋白将大染色质结构域的重塑与基因表达的调节整合在一起。这个项目将阐明控制表皮细胞细胞核中基因重组的机制，并将有助于更好地理解干细胞驱动的器官再生的原理。该项目的成功将对在干细胞治疗和再生医学方面建立新的方法方面取得进展具有重要意义。

With major progress being made in tissue engineering and organ regeneration, it is important to understand how the expression of genes in stem cells leads to their development into specialised cell types. Skin epithelium is a self-renewing biological structure that consists of the stem cells residing in the basal layer and differentiating into keratinocytes of suprabasal layers. This process results in a formation of an epidermal barrier protecting organisms from harmful environmental factors and is accompanied by activation of a number of epidermis-specific genes, located in the genome as clusters on four distinct chromosomes. However, it is unclear how these clusters are distributed in the nuclei of epidermal cells and what regulates their intra-nuclear arrangements and activity. We will test whether this process is regulated by a specific Satb1 protein that intergrates remodeling of large chromatin domains with regulation of gene expression.This project will shed light on the mechanisms that control gene reorganisation in the nuclei of epidermal cells and will be useful for better understanding the principles of stem cell-driven organ regeneration. Success of this project will be important for the progress in establishing new approaches in stem cell-based therapy and regenerative medicine.