Bat pluripotent stem cells as a novel experimental system

蝙蝠多能干细胞作为一种新型实验系统

• 批准号: 10592777
• 负责人: Thomas P. Zwaka
• 金额: $ 25.35万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-14 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10592777
• 关键词: Address; Affect; Animal Model; Anti-Inflammatory Agents; Biological Models; Biology; Breeding; COVID-19; CRISPR/Cas technology; Cell Differentiation process; Cell Line; Cell model; Cells; Chiroptera; Clustered Regularly Interspaced Short Palindromic Repeats; Complex; Data; Ebola; Echolocation; Engineering; Enzymes; Evolution; Genes; Genetic study; Goals; Immune; Immune Tolerance; Immune response; Immune system; Immunity; In Vitro; Inflammasome; Inflammatory; Inflammatory Response; Knock-out; Longevity; Mammals; Metabolic; Metabolism; Modeling; Molecular; Myeloid Cells; Natural Immunity; Organoids; Outcome; Pathway interactions; Physiology; Play; Pluripotent Stem Cells; Property; Protocols documentation; Radiation; Readiness; Research; Research Proposals; Role; Sampling; Series; Severe Acute Respiratory Syndrome; System; Testing; Tissues; Viral load measurement; Virus; Virus Diseases; Work; cell immortalization; cell type; cellular pathology; fascinate; fly; forward genetics; genetic testing; healthspan; induced pluripotent stem cell; insight; ketogenesis; ketogentic; marenostrin; metabolomics; model organism; novel; programs; response; stem cells; tool; transcriptomics; tumorigenesis; viral outbreak

Bats are perhaps the most fascinating but least understood mammalian order. It is clear that, although bats are a critically needed new model organism, limited access to animal and cell models has hindered their study. We recently generated the first induced pluripotent stem cells (iPSCs) from a bat (R. ferrumequinum) and discovered that bat iPSCs had a unique transcriptomic profile enriched in metabolomic and immune pathways ketogenic metabolism and a unique inflammasome response. We plan to generate additional to test if our novel protocol can be used for any bat species and that essential metabolic genes uniquely expressed only in bat cells, including HMGC2, can be knocked out using CRISPR/Cas9. We will also evaluate if the inflammatory response is altered in myeloid cells derived from bat iPSCs. Bat stem cell lines and differentiated progeny will help address bat physiology’s most tantalizing questions, including immunity.

蝙蝠也许是最迷人的，但最不了解的哺乳动物。显然 虽然蝙蝠是一种急需的新模式生物，但对动物的接触有限， 和细胞模型阻碍了他们的研究。我们最近制造了第一个 来自蝙蝠的多能干细胞（iPSC）（R.发现蝙蝠 iPSC具有独特的转录组学特征，在代谢组学和免疫学方面富集。 生酮代谢途径和独特的炎性反应。我们计划 产生额外的测试，如果我们的新协议可以用于任何蝙蝠物种， 仅在蝙蝠细胞中表达的必需代谢基因，包括HMGC 2， 使用CRISPR/Cas9进行敲除。我们还将评估炎症反应是否 在源自蝙蝠iPSC的骨髓细胞中发生了改变。蝙蝠干细胞系和分化 后代将有助于解决蝙蝠生理学上最诱人的问题，包括 免疫力