Allorecognition, parasitic stem cells and regeneration in a basal chordate

基底脊索动物的同种识别、寄生干细胞和再生

• 批准号: 10557096
• 负责人: Anthony W De Tomaso
• 金额: $ 51.41万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10557096
• 关键词: Award; Biological; Biological Assay; Biological Models; Blood Vessels; Bone Marrow Transplantation; Cardiovascular system; Cells; Chordata; Endocrine; Event; Funding; Germ cell tumor; Goals; Grant; Growth; Homing; Human; Immunity; Immunology; Individual; Mediating; Molecular; Natural regeneration; Normal Cell; Organism; Peripheral; Phenotype; Process; Property; Reaction; Regenerative response; Research; Resources; Specificity; Transplantation; Work; autocrine; cancer cell; cell regeneration; follow-up; germline stem cells; innovation; insight; novel; novel strategies; prevent; programs; response to injury; stem cell biology; stem cell niche; stem cells; tissue regeneration; transmission process

Abstract Our lab works at the intersection of immunology, stem cell biology and regeneration, and the grants funding this work (GM123267 and GM 123255) which we are requesting to merge in the MIRA program have provided numerous insights into the molecular mechanisms underlying both self/non-self recognition, as well as a genetically determined cell competition event that occurs between mobile germline stem cells for niche occupancy. In addition, we have recently found that these same germline stem cells, which are lineage restricted under normal conditions, are responsible for a regenerative response to injury called Whole Body Regeneration, during which entire bodies, including all cardiovascular, GI, central and peripheral nervous, endocrine and germline tissues are regenerated de novo from isolated vascular fragments, and we propose to extend our research efforts into this robust model system of chordate regeneration. As described in the proposal, in the last 18 months, these studies have led to a number of exciting findings we will follow-up on during the upcoming funding period, including: dissecting the molecular basis for allorecognition specificity and its conservation with vertebrate immunity; a novel mechanism of autocrine stimulation that is required for homing of germline stem cells and likely plays a role in the competitive phenotype; and rescue and lineage tracing assays for whole body regeneration that have revealed that a single germline stem cell can give rise to an entire body- a result which may have major implications for understanding germ cell tumors, and also provides a unique opportunity for rapidly creating genetically modified lines of Botryllus. Our long-term goals are to utilize the unique biological properties of Botryllus to carry out innovative molecular mechanistic studies, and a MIRA award would allow us to redirect our efforts from funding to carrying out more and better innovative research on these biomedically important topics.

摘要