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The Axolotl as a system to define the function and evolution of reprogramming activities

蝾螈作为一个系统来定义重编程活动的功能和进化

基本信息

批准号：
66107129
负责人：
Professorin Dr. Elly Margaret Tanaka, Ph.D.
金额：
--
依托单位：
IMBA - Institute of Molecular Biotechnology GmbH
依托单位国家：
德国
项目类别：
Priority Programmes
财政年份：
2008
资助国家：
德国
起止时间：
2007-12-31 至 2014-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/66107129?language=en
关键词：
Axolotl system define function evolution

项目摘要

Non-mammalian model organisms have been critical in mechanistically dissecting biological processes and identifying the essential, conserved function of genes. It was unknown whether non-mammalian OCT4 and SOX2 orthologs can reprogram cells to pluripotency. The Axolotl is an ideal non-mammalian model to analyze the conservation of OCT4/SOX2 driven reprogramming. AxOCT4 can sustain mouse ES cells. Furthermore the Axolotl is an experimentally accessible model where totipotent germ cells form by embryonic induction. Finally the Axolotl undertakes regeneration that involves reprogramming cells to less committed states.In the last period we showed that AxOCT4 and AxSOX2 can reprogram human fibroblasts to pluripotency. We also showed that OCT4+SOX2+ cells arise in the regenerating spinal cord where cells rebuild functional tissues. Finally, we identified chromatin proteins expressed in regenerating and not wounded tissue likely involved in reprogramming.Here we will further study AxOCT4, AxSOX2 and other factors in reprogramming. First, we will isolate spinal cord OCT4+SOX2+ cells, test their potency, and test the role of OCT4 and our chromatin factors in reprogramming these cells. Second, we will characterize putative ES-like cells cultured from the Axolotl. Finally, we will use transcriptome analysis to compare AxOCT4+SOX2+ cells from atleast three different sources including epiblast and regenerating spinal cord to define the overlapping and non-overlapping gene sets. Comparing this data to the mammalian pluripotency network will refine our understanding of subnetworks required for full pluripotency versus partially reprogrammed states.

非哺乳动物模式生物在机械解剖生物过程和识别基因的基本保守功能方面至关重要。目前尚不清楚非哺乳动物OCT 4和SOX 2直系同源物是否可以将细胞重编程为多能性。蝾螈是分析OCT 4/SOX 2驱动重编程保守性的理想非哺乳动物模型。AxOCT 4可以维持小鼠ES细胞。此外，蝾螈是一种实验可及的模型，其中全能生殖细胞通过胚胎诱导形成。最后，蝾螈进行再生，包括将细胞重编程为不太定型的状态。在上一阶段，我们发现AxOCT 4和AxSOX 2可以将人类成纤维细胞重编程为多能性。我们还表明，OCT 4 + SOX 2+细胞出现在再生脊髓中，其中细胞重建功能组织。最后，我们鉴定了在再生组织和未受伤组织中表达的可能参与重编程的染色质蛋白。在这里，我们将进一步研究AxOCT 4，AxSOX 2和其他重编程因子。首先，我们将分离脊髓OCT 4 + SOX 2+细胞，测试它们的效力，并测试OCT 4和我们的染色质因子在重编程这些细胞中的作用。其次，我们将表征从蝾螈中培养的推定ES样细胞。最后，我们将使用转录组分析来比较来自至少三个不同来源的AxOCT 4 + SOX 2+细胞，包括外胚层和再生脊髓，以定义重叠和非重叠基因集。将这些数据与哺乳动物多能性网络进行比较，将使我们更好地理解完全多能性与部分重编程状态所需的子网络。