Control of stem cell proliferation in the arabidopsis root

干细胞是可以产生许多其他细胞的祖细胞，是所有多细胞生物发育的核心，因为它们提供非特化（或未分化）细胞的自我维持库，为组织和器官的形成提供前体细胞。因此，干细胞的维持对所有多细胞生物都是至关重要的，对医学和农业的再生生物学具有重要意义。考虑到干细胞的终身重要性，它们被安全地藏在所谓的干细胞壁龛中，以避免受到伤害，这些壁龛提供了一个微环境，促进细胞的自我更新，抑制细胞分化。细胞分化与细胞不再是干细胞，获得特化细胞类型的身份和停止细胞分裂有关。植物干细胞生态位位于根和茎尖的分生组织中，在整个植物生命周期中对新器官和组织的产生至关重要，在某些物种中可以跨越数千年。分生组织也是植物细胞分裂的主要部位，并最终负责植物的大部分生长以及对环境信号和胁迫的可塑性调节。在拟南芥的根分生组织中，所有不同根细胞类型的干细胞围绕着一小群被称为静止中心的组织细胞，它们一起形成了一个干细胞生态位。虽然我们知道许多基因是干细胞功能所必需的，它们决定了干细胞的身份，但我们对如何控制干细胞的分裂知之甚少。视网膜母细胞瘤相关蛋白（RBR）存在于动物和植物中，在哺乳动物中，其缺失与癌细胞增殖有关。最近有研究表明RBR控制植物根分生组织的干细胞分裂（Wildwater et al., 2005, the RETINOBLASTOMA-RELATED Gene regulating stem cell Maintenance in Arabidopsis Roots’cell 123: 1337/1349）。RBR缺失会增加干细胞数量，而RBR水平的增加会导致干细胞分化和干细胞身份的丧失。然而，由于RBR存在于所有细胞中，我们不知道RBR是如何以不同的方式调节来控制根中不同类型干细胞的分裂的。控制RBR活性的一个已知因素是一组被称为d型细胞周期蛋白（CYCD）的蛋白质。在人类中只有三种，但是植物有更多的不同的cycd——在典型的杂草植物拟南芥中有10种。在尚未发表的工作中，我们发现不同类型的干细胞在根中表达不同的CYCD基因，这为如何实现对其增殖的独立控制提供了解释。我们还发现，在缺乏单个CYCD基因的突变体中，特定根干细胞的增殖受到损害。在本提案中，我们将以这些初步结果为基础，并将测试不同干细胞群体的增殖取决于通过RBR途径作用的特定CYCD基因的假设。我们还将开展CYCD基因调控的实验，并测试所有CYCD基因是否具有相同的功能。因此，我们将了解植物根部如何调节干细胞分裂，这可能对其他位置和其他类型生物的干细胞具有普遍意义。

Stem cells are progenitor cells from which many other cells can arise, and are central to the development of all multicellular organisms because they provide a self-maintaining reservoir of unspecialized (or undifferentiated) cells that supply the precursor cells for tissue and organ formation. The maintenance of stem cells is therefore crucial for all multicellular organisms and is of outstanding significance for regenerative biology in medicine and agriculture. Given the life-long importance of stem cells, they are tucked safely from harm's way, in so-called stem cell niches that provide a microenvironment promoting self-renewal of the cells and inhibiting cell differentiation. Cell differentiation is associated with a cell ceasing to be a stem cell, acquiring the identity of a specialised cell type and stopping cell division. Plant stem cell niches are located in meristems at root and shoot tips, and are pivotal to the production of new organs and tissues throughout the plant life cycle that in some species can span several thousand years. Meristems are also major sites of cell division in plants, and are ultimately responsible for most of the growth of plants as well as the plastic modulation of growth in response to environmental signals and stress. In the Arabidopsis root meristem, stem cells for all the different root cell types surround a small group of organizing cells called the quiescent center, and together they form a stem cell niche. Although we know a number of genes that are required for stem cell function and which define stem cell identity, we have very little understanding of how the division of stem cells is controlled. The retinoblastoma-related (RBR) protein is found in animals and plants, and in mammals its loss is associated with cancerous cell proliferation. Recently it has been shown that RBR controls stem cell division in the root meristem of plants (Wildwater et al., 2005 'The RETINOBLASTOMA-RELATED Gene Regulates Stem Cell Maintenance in Arabidopsis Roots' Cell 123: 1337/1349). Loss of RBR increases stem cell number whereas increasing RBR levels results in their differentiation and loss of stem cell identity. However, we do not know how RBR is regulated differently to control division of the different types of stem cell in the root, because it is present in all of the cells. One factor known to control RBR activity is a group of proteins known as D-type cyclins (CYCD). In humans there are only three of these, but plants have much larger numbers of different CYCDs- ten in the model weed plant Arabidopsis. In work still unpublished, we have discovered that different stem cell types in the root express different CYCD genes, providing an explanation of how independent control of their proliferation can be achieved. We also find that in mutants lacking individual CYCD genes the proliferation of specific root stem cells is compromised. In this proposal, we build on these initial results and will test the hypothesis that proliferation of different stem cell populations depends on specific CYCD genes acting through the RBR pathway. We will also carry out experiments to address how the CYCD genes are regulated, and test whether all CYCD genes have equivalent functions. As a result, we will understand how stem cell division is regulated in the plant root, which is likely to have general implications for stem cells in other positions and other types of organism.