染色质重塑介导根干细胞编程和重编程的分子机制

Stem cells are a group of undifferentiated cells which are able to self-renew and differentiate into distinct cell types. Root is one of the most important organs of plants and its growth and development depends on continuous cell division and differentiation of the stem cells situated in root meristem. Recent data suggest that chromatin modification factors, other than transcription factors, also play a vital role in stem cell fate determination. However, the molecular mechanism of how transcription factors and chromatin modification factors act together to regulate stem cell pluripotency still remains poorly understood. Previously, we have shown that WOX5 as a central root stem cell regulator is not only required for stem cell maintenance, but also can reprogram highly differentiated columella cells into columella stem cells in Arabidopsis. Taking advantage of this reprogramming property, we carried out a genetic screen for the suppressors of WOX5 overexpression and isolated a mutant named swo1. We further found that the casual gene encodes an ATP-dependent chromatin remodeling factor which thus far, has not been characterized in plant stem cell regulation. Based on these new findings, we will use approaches that combine genetics, molecular biology, biochemistry and cell type-specific transcriptomics to unravel how chromatin remodeling mediates root stem cell programming and reprogramming by WOX5, which will provide novel insight into the molecular basis of plant stem cell pluripotency.

干细胞是一类可自我更新并可特化为不同细胞类型的未分化细胞。根是植物最重要的器官之一，它的生长和发育依赖于根尖干细胞的持续性分裂和分化。近年来的研究表明，除了转录因子之外，染色质修饰因子也在干细胞命运决定中发挥非常重要的作用。然而，转录因子和染色质修饰因子如何协同控制根干细胞多能性的机制还很不清楚。我们以前的研究结果显示，拟南芥根干细胞的中心调控因子WOX5不仅是维持干细胞所必需的，而且可以把高度分化的小柱细胞重编程成小柱干细胞。在此基础上，我们通过遗传筛选得到一个能抑制WOX5重编程能力的突变体swo1。我们进一步发现，SWO1基因编码了一个还未曾被报道作用于干细胞调控的ATP依赖型染色质重塑因子。本项目拟以此为基础，综合运用遗传学、分子生物学、生物化学和细胞类型特异转录组学等手段，解析染色质重塑是如何介导WOX5对干细胞编程和重编程的作用，深入理解植物干细胞多能性的分子基础。

干细胞是一类可自我更新并可特化为不同细胞类型的未分化细胞。干细胞的分裂为植物器官的形成持续不断的提供新细胞。除了转录因子之外，染色质修饰因子也在干细胞命运决定中发挥非常重要的作用。然而，这两类因子如何协同控制植物干细胞多能性的机制还很不清楚。我们已发表的结果表明转录因子WUSCHEL-RELATED HOMEOBOX 5 (WOX5)在植物根尖干细胞编程和重编程中发挥了关键作用。在这项后续研究中，我们通过遗传筛选获得了一WOX5过量表达的抑制子suppressor of WOX5 overexpression 1 (swo1)。通过BSA分析和图位克隆，发现SWO1编码了一ATP依赖型的染色质重塑因子。我们的研究表明SWO1不仅是WOX5诱导的干细胞重编程所必需的，而且也是根尖干细胞巢维持的重要因子。遗传学、分子生物学和组学的分析表明WOX5和SWO1作用于同一途径控制下游干细胞特化程序。进一步的生化证据证明，SWO1和WOX5形成蛋白复合体发挥调控干细胞的功能。最后，我们也阐明SWO1还能和WUS结合，维持茎尖干细胞的多能性。总之，我们的研究揭示了一种基于染色质重塑的且在茎尖和根尖都保守的干细胞调控新机制。