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的重大进展，重要的是要了解干细胞中基因的表达如何导致它们发育成专门的细胞类型。皮肤上皮是一种自我更新的生物结构，由基底层的干细胞分化为基底层上的角质形成细胞组成。这一过程导致形成表皮屏障，保护生物体免受有害环境因素的影响，并伴随着许多表皮特异性基因的激活，这些基因以簇的形式位于基因组中的四条不同染色体上。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，是什么调节其核内的安排和活动。我们将测试这一过程是否是由一个特定的Satb1蛋白，整合与调控基因expression.This项目的染色质大域的重塑将揭示控制基因重组在表皮细胞核的机制，并将有助于更好地理解干细胞驱动的器官再生的原则。该项目的成功将对建立基于干细胞的治疗和再生医学新方法的进展至关重要。

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.