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

描述（由申请人提供）：脂肪组织基质血管组分（SVF）是可从棕色和白色脂肪组织中分离的多能间充质干细胞的来源。虽然它是公认的前体细胞，产生成熟的脂肪组织驻留在SVF，多能脂肪干细胞能够自我更新尚未被分子定义。我们的初步数据表明，小鼠端粒酶逆转录酶表达（mTert）标志着一个群体的棕色和白色脂肪SVF细胞表达假定的脂肪前体细胞表面标志物，能够自我更新和体外脂肪分化。此外，mTert细胞谱系从3周龄至6月龄在体内棕色和白色脂肪组织中是静止的，然而高脂肪饮食导致8月龄动物中mTert谱系增殖增加。基于这些发现，该项目旨在测试新的假设，即mTert表达细胞是多能脂肪干细胞，能够响应高脂肪饮食和β-肾上腺素能刺激，作为分化线索。有两个具体目标：1）体外mTert表达细胞的功能和分子表征，将这些推定的脂肪干细胞与定向祖细胞进行比较; 2）与来自PDGFrα-CreERT 2小鼠的定向祖细胞相比，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机制将对理解脂肪组织发育和肥胖具有重要意义，这些知识可能适用于人类疾病或损伤的自体组织移植。

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.