Kinetics of cell division in normal and malignant epidermis

正常和恶性表皮细胞分裂的动力学

• 批准号: G0601740/1
• 负责人: Benjamin Simons
• 金额: $ 13.08万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0601740%2F1
• 关键词: Kinetics; cell; division; normal; malignant

All biological tissues, such as skin, are made from cells. Amongst the variety of different cell types, stem cells assume a very special role retaining the ability to produce identical copies of themselves when they divide, and to turn into function-specific cells, a process known as differentiation. As such, stem cells are crucial for development and are expected to play a key role in tissue maintenance and repair. Typically, each tissue is comprised of many different cell types, each having a specific function. One of the main challenges in biological sciences is to understand how stem cells and their progeny function to maintain tissue. However, studies of cellular organisation of tissue do not reveal the lineage of cells, i.e. it is often difficult to distinguish stem cells from other cell types and impossible to trace the ancestry of a given cell.This proposal is designed to take advantage of modern genetic labelling techniques to study cell fate in the epidermis, the outer most layers of skin, and in other tissue types. By genetic modification of the DNA, a strain of mice can be developed where a fraction of skin cells can be induced to express a yellow fluorescent protein, allowing they and their progeny to be detected under the microscope as patches of yellow-stained cells. By counting the number of cells in these labelled cell clusters, known as clones, methods of statistical analysis, more familiar in the realm of physical and mathematical sciences, can be applied to reveal different cell types, cell division rates and pathways and, ultimately, to resolve the mechanism of epidermal maintenance. Intriguingly, recent studies using these techniques have revealed that the epidermis conforms to a remarkably simple random process involving only one type of dividing cell population, overturning a long-held dogma in the scientific literature. These preliminary studies provide a platform to investigate tissue maintenance in other systems, such as humans and frogs, and to explore in detail the mechanism of early tumour growth and the effects of drug delivery.

所有生物组织，例如皮肤，都是由细胞构成的。在各种不同的细胞类型中，干细胞扮演着非常特殊的角色，在分裂时保留产生相同副本的能力，并转变为功能特异性细胞，这一过程称为分化。因此，干细胞对于发育至关重要，并有望在组织维护和修复中发挥关键作用。通常，每个组织都由许多不同的细胞类型组成，每种细胞类型都有特定的功能。生物科学的主要挑战之一是了解干细胞及其后代如何发挥维持组织的功能。然而，组织细胞组织的研究并不能揭示细胞的谱系，即通常很难将干细胞与其他细胞类型区分开来，并且不可能追踪给定细胞的祖先。该提案旨在利用现代基因标记技术来研究表皮、皮肤最外层和其他组织类型中的细胞命运。通过对 DNA 进行基因改造，可以培育出一种小鼠品系，其中的一小部分皮肤细胞可以被诱导表达黄色荧光蛋白，从而使它们及其后代能够在显微镜下以黄色染色细胞斑块的形式被检测到。通过计算这些标记细胞簇（称为克隆）中的细胞数量，可以应用物理和数学科学领域更为熟悉的统计分析方法来揭示不同的细胞类型、细胞分裂速率和途径，并最终解决表皮维持的机制。有趣的是，最近使用这些技术的研究表明，表皮符合一个非常简单的随机过程，仅涉及一种类型的分裂细胞群，推翻了科学文献中长期存在的教条。这些初步研究提供了一个平台来研究其他系统（例如人类和青蛙）的组织维持，并详细探索早期肿瘤生长的机制和药物输送的影响。