Control of stem cell proliferation in the arabidopsis root

拟南芥根干细胞增殖的控制

• 批准号: BB/E022383/2
• 负责人: James Murray
• 金额: $ 26.64万
• 依托单位: CARDIFF UNIVERSITY
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE022383%2F2
• 关键词: Control; stem; cell; proliferation; arabidopsis

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.

干细胞是可以产生许多其他细胞的祖细胞，并且是所有多细胞生物体发育的核心，因为它们提供了一个自我维持的非特化（或未分化）细胞库，为组织和器官形成提供前体细胞。因此，干细胞的维持对所有多细胞生物至关重要，并且对医学和农业中的再生生物学具有突出的意义。鉴于干细胞的终身重要性，它们被安全地隐藏在所谓的干细胞龛中，这些干细胞龛提供了一个促进细胞自我更新和抑制细胞分化的微环境。细胞分化与细胞不再是干细胞、获得特化细胞类型的身份并停止细胞分裂有关。植物干细胞生态位位于根和茎尖的分生组织中，并且在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场所，并且最终负责植物的大部分生长以及响应于环境信号和胁迫的生长的可塑性调节。在拟南芥根分生组织中，所有不同类型根细胞的干细胞围绕着一小群组织细胞，称为静止中心，它们一起形成干细胞小生境。虽然我们知道干细胞功能所需的一些基因，并确定干细胞的身份，我们对干细胞的分裂是如何控制的了解很少。视网膜母细胞瘤相关（RBR）蛋白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，已经表明RBR控制植物的根分生组织中的干细胞分裂（Wildwater等人，2005“视网膜母细胞瘤相关基因调节拟南芥根中的干细胞维持"Cell 123：1337/1349）。RBR的丧失增加干细胞数量，而RBR水平的增加导致其分化和干细胞身份的丧失。然而，我们不知道RBR是如何以不同的方式调节以控制根部不同类型干细胞的分裂的，因为它存在于所有细胞中。已知控制RBR活性的一个因素是一组称为D型细胞周期蛋白（CYCD）的蛋白质。人类只有三种，但植物有更多的不同CYCD-在模式杂草植物拟南芥中有十种。在尚未发表的工作中，我们发现根中不同类型的干细胞表达不同的CYCD基因，这为如何独立控制其增殖提供了解释。我们还发现，在突变体缺乏个别CYCD基因的增殖特定的根干细胞受到损害。在这个提议中，我们建立在这些初步结果的基础上，并将测试不同干细胞群体的增殖取决于特定CYCD基因通过RBR途径起作用的假设。我们还将进行实验，以解决CYCD基因是如何调节的，并测试是否所有CYCD基因都具有相同的功能。因此，我们将了解干细胞分裂是如何在植物根中调节的，这可能对其他位置和其他类型的生物体中的干细胞具有普遍意义。

项目成果

Re-induction of the cell cycle in the Arabidopsis post-embryonic root meristem is ABA-insensitive, GA-dependent and repressed by KRP6.

• DOI: 10.1038/srep23586
• 发表时间: 2016-03-29
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Nieuwland J;Stamm P;Wen B;Randall RS;Murray JA;Bassel GW
• 通讯作者: Bassel GW

D-type cyclins control cell division and developmental rate during Arabidopsis seed development.

• DOI: 10.1093/jxb/ers015
• 发表时间: 2012-06
• 期刊: Journal of experimental botany
• 影响因子: 6.9
• 作者: Collins C;Dewitte W;Murray JA
• 通讯作者: Murray JA

WOX5 suppresses CYCLIN D activity to establish quiescence at the center of the root stem cell niche.

• DOI: 10.1016/j.cub.2014.07.019
• 发表时间: 2014-08-18
• 期刊: CURRENT BIOLOGY
• 影响因子: 9.2
• 作者: Forzani, Celine;Aichinger, Ernst;Sornay, Emily;Willemsen, Viola;Laux, Thomas;Dewitte, Walter;Murray, James A. H.
• 通讯作者: Murray, James A. H.

Seed size plasticity in response to embryonic lethality conferred by ectopic CYCD activation is dependent on plant architecture.

• DOI: 10.1080/15592324.2016.1192741
• 发表时间: 2016-07-02
• 期刊: Plant signaling & behavior
• 影响因子: 2.9
• 作者: Sornay E;Dewitte W;Murray JA
• 通讯作者: Murray JA

A bistable circuit involving SCARECROW-RETINOBLASTOMA integrates cues to inform asymmetric stem cell division.

• DOI: 10.1016/j.cell.2012.07.017
• 发表时间: 2012-08-31
• 期刊: Cell
• 影响因子: 64.5
• 作者: Cruz-Ramírez A;Díaz-Triviño S;Blilou I;Grieneisen VA;Sozzani R;Zamioudis C;Miskolczi P;Nieuwland J;Benjamins R;Dhonukshe P;Caballero-Pérez J;Horvath B;Long Y;Mähönen AP;Zhang H;Xu J;Murray JA;Benfey PN;Bako L;Marée AF;Scheres B
• 通讯作者: Scheres B