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Maintenance of Stem Cell Pluripotency in Pigs with Interleukin-6

用 IL-6 维持猪干细胞多能性

基本信息

批准号：
9750253
负责人：
Alan D Ealy
金额：
$ 19.82万
依托单位：
VIRGINIA POLYTECHNIC INST AND ST UNIV
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9750253
关键词：
Abbreviations Anatomy Apoptosis Biomedical Research Cell Culture Techniques Cell Maintenance Cell Proliferation Cells ES Cell Line Embryo Embryology Exhibits Family member Family suidae Fibroblasts Genetic Engineering Germ Layers Glycogen Synthase Kinases Goals Human IL6ST gene Immunologics Inner Cell Mass Interleukin-6 LIF gene MAP2K1 gene Maintenance Mammals MicroRNAs Mitogen-Activated Protein Kinase Kinases Modeling Mus Organ PI3K/AKT Pharmacology Physiological Pluripotent Stem Cells Population Regenerative Medicine Regulation Reporting Research Personnel STAT3 gene Signal Pathway Somatic Cell Source Stat3 protein Stem cells Supplementation Teratoma Testing Tissues Transgenes Work Xenograft procedure cytokine embryonic stem cell human disease induced pluripotent stem cell innovation interleukin-6 receptor alpha pluripotency self-renewal stem cell biology stem cell population transcription factor transgene expression

项目摘要

Project Summary Pigs are physiologically, anatomically and immunologically similar to humans. Thus, they serve as a great biomedical research model. However, the inability to generate embryonic stem cells (ESCs) and somatic cell reprogrammed induced pluripotent stem cells (iPSCs) has limited the usefulness of this model species for studying human diseases and regenerative medicine. Overcoming this limitation will enhance opportunities to generate genetically-engineered lines that can be used for studying human diseases. The long-term goal of this work is to establish innovative approaches for maintaining porcine ESCs and iPSCs without the need to constitutively express pluripotency-related transcriptional factors. The innovative strategy tested in this exploratory proposal is using interleukin-6 (IL6) to maintain pluripotency in porcine cells. Interleukin-6 has not been tested as a pluripotency factor in pigs, but all indications are that it will serve in this capacity. Previous reports and recent findings provide compelling evidence that IL6 serves as a pluripotency factor in pigs, humans and other mammals. The work in this proposal will test the hypothesis that IL6 is a driver of plasticity and pluripotency in porcine ESCs and iPSCs. Two aims are planned. Aim 1 will explore the actions of IL6 acts on porcine ICM cells. The premise is that IL6 will maintain a self-renewing population of pICM cells that resemble the authentic pluripotency features of naïve ESCs. Aim 2 will examine whether transgene-free porcine iPSC can be established by IL6 supplementation. Reprogramming porcine fibroblasts in the presence of IL6 is anticipated to reduce the need for transgene expression of core pluripotency factors and microRNAs that facilitate pluripotency in pigs.

项目摘要猪在生理学、解剖学和免疫学上与人类相似。因此，他们服务于作为一个伟大的生物医学研究模型。然而，无法产生胚胎干细胞胚胎干细胞（ESCs）和体细胞重编程诱导多能干细胞（iPSCs）的研究限制了这种模式物种对研究人类疾病和再生医学的有用性。克服这一限制将增加产生基因工程品系的机会可以用来研究人类疾病。这项工作的长期目标是建立用于维持猪ESC和iPSC的创新方法，组成型表达多能性相关转录因子。创新战略在这个探索性的提议中测试的是使用白细胞介素-6（IL-6）来维持猪细胞白细胞介素-6还没有被测试为猪的多能性因子，但所有有迹象表明，它将担任这一职务。以前的报告和最近的调查结果提供了令人信服的证据表明，IL 6在猪，人和其他动物中作为多能性因子哺乳动物这项提案中的工作将检验IL 6是可塑性驱动因素的假设，在猪ESC和iPSC中的多能性。计划有两个目标。目标1将探讨 IL 6作用于猪ICM细胞。前提是IL 6将维持自我更新的种群 pICM细胞类似于幼稚ESC的真实多能性特征。目标2将检查是否可以通过补充IL 6建立无转基因猪iPSC。预期在IL 6存在下重编程猪成纤维细胞可减少对细胞因子的需要。核心多能性因子和微RNA的转基因表达促进了多能性，猪