Telomerase as a Marker of Brown and White Adipose Tissue Stem Cells

端粒酶作为棕色和白色脂肪组织干细胞的标记

• 批准号: 8718295
• 负责人: MATTHEW D LYNES
• 金额: $ 5.33万
• 依托单位: JOSLIN DIABETES CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8718295
• 关键词: 2,4-thiazolidinedione; Adipocytes; Adipose tissue; Adrenergic Agents; Adrenergic beta-Agonists; Adult; Age; Animals; Autologous; Autologous Transplantation; Behavior; Blood Vessels; Brown Fat; Cartilage; Cell Differentiation process; Cell Fraction; Cell Lineage; Cell Maintenance; Cell Proliferation; Cell Transplantation; Cell surface; Cells; Centrifugation; Collaborations; Commit; Cues; Data; Development; Diet; Energy Metabolism; Fatty acid glycerol esters; Gene Expression; Generations; Goals; Health; Hematopoietic; Histocompatibility Testing; Histocytochemistry; Homeostasis; Human; In Vitro; Injury; Insulin Resistance; Intestines; Knowledge; Laboratories; Lead; Lipids; Longitudinal Studies; Luciferases; Mediating; Mesenchymal; Mesenchymal Stem Cells; Molecular; Mus; Muscle; Nerve Tissue; Non-Insulin-Dependent Diabetes Mellitus; Normal tissue morphology; Obesity; Organ; Pattern; Play; Population; Proliferating; Public Health; Radiation Injuries; Reporter; Research Proposals; Role; Sorting - Cell Movement; Source; Stem cells; System; Telomerase; Testing; Thiazolidinediones; Tissues; Transgenic Animals; Transplanted tissue; adrenergic; base; design; human disease; in vivo; in vivo imaging; multipotent cell; novel; novel strategies; osteogenic; precursor cell; regenerative; research study; response; response to injury; self-renewal; telomerase reverse transcriptase

DESCRIPTION (provided by applicant): Adipose tissue stromal vascular fraction (SVF) is a source of multipotent mesenchymal stem cells that can be isolated from brown and white adipose tissue. While it is accepted that the precursor cells that give rise to mature adipose tissue reside in the SVF, multipotent adipose stem cells capable of self-renewal have not been molecularly defined. Our preliminary data show that mouse telomerase reverse transcriptase expression (mTert) marks a population of brown and white adipose SVF cells expressing putative adipogenic precursor cell surface markers that are capable of self-renewal and adipogenic differentiation in vitro. Further, the mTert cellular lineage is quiescent in brown and white adipose tissue in vivo from 3 weeks of age until 6 months, however high fat diet caused an increase in mTert lineage proliferation in 8-month old animals. Based on these findings, this project is designed to test the novel hypothesis that mTert expressing cells are multipotent adipose stem cells capable of responding to high fat diet and beta-adrenergic stimulation that serve as differentiation cues. There are two specific aims: 1) Functional and molecular characterization of mTert- expressing cells in vitro comparing these putative adipose stem cells to committed progenitor cells; 2) Determine the effects of differentiation cues on mTert cell proliferation and differentiation in adipose in vivo compared to committed progenitor cells from PDGFrα-CreERT2 mice. Identifying adipose tissue stem cells and the mechanisms that govern their proliferation and differentiation will have important significance in the understanding of adipose tissue development and obesity and this knowledge may be applicable in autologous tissue transplants in human disease or injury.

描述（由申请人提供）：脂肪组织基质血管组分（SVF）是多能间充质干细胞的来源，可以从棕色和白色脂肪组织中分离出来。虽然人们普遍认为成熟脂肪组织的前体细胞存在于SVF中，但能够自我更新的多能脂肪干细胞尚未被分子定义。我们的初步数据表明，小鼠端粒酶逆转录酶表达（mTert）标志着棕色和白色脂肪SVF细胞群体表达假定的脂肪生成前体细胞表面标记物，能够在体外自我更新和脂肪生成分化。此外，从3周龄到6个月大，mTert细胞系在体内棕色和白色脂肪组织中处于静止状态，然而高脂肪饮食导致8个月大动物的mTert细胞系增殖增加。基于这些发现，本项目旨在验证新的假设，即表达mTert的细胞是多能脂肪干细胞，能够对高脂肪饮食和β -肾上腺素能刺激做出反应，作为分化线索。有两个特定的目的：1)在体外比较mTert-表达细胞的功能和分子特性，将这些假定的脂肪干细胞与固定的祖细胞进行比较；2)与PDGFrα-CreERT2小鼠的固定祖细胞相比，确定分化线索对体内脂肪中mTert细胞增殖和分化的影响。识别脂肪组织干细胞及其增殖和分化的调控机制对了解脂肪组织发育和肥胖具有重要意义，这一知识可能适用于人类疾病或损伤的自体组织移植。