Identification of adipose NG2+ cells as a novel bipotent precursor of pericytes and adipocytes

鉴定脂肪 NG2 细胞作为周细胞和脂肪细胞的新型双能前体

• 批准号: RGPIN-2016-06610
• 负责人: Sung, HoonKi
• 金额: $ 2.26万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=683900
• 关键词: Identification; adipose; NG2+; cells; novel

Brown adipose tissue (BAT) and white adipose tissue (WAT) are the two major mammalian fat tissues that have evolved to adapt to various environmental challenges by developing specialized metabolic functions. While BAT generates heat through non-shivering thermogenesis, WAT stores excess energy or releases lipid in response to metabolic demand, playing an essential role in metabolic homeostasis. The overall goal of my research group is to understand the mechanisms of adipose plasticity by which adipose tissues adapt to environmental and metabolic challenges. Prolonged energy surplus often requires new adipocyte generation (adipogenesis) from the progenitor reservoir with concomitant new vessel formation (angiogenesis). Recent studies have shown that adipocyte precursor cells reside within the WAT in the proximity of the adipose vasculature, suggesting the interplay of adipogenesis in coordination with angiogenesis. Yet, a basic understanding of how these dynamic processes are regulated is still unclear. Interestingly, our recent data suggests that Neural-Glial antigen-2 positive (NG2+) cells contribute to both white adipocytes and vascular pericytes, cells that are involved in new vessel formation, suggesting a key regulatory role of NG2+ cells in both adipogenesis and angiogenesis. Therefore, in the current proposal, we propose to characterize the developmental potential of adipose NG2+ cells and their functional contribution to both adipocytes and vascular pericytes by utilizing flow cytometry and fate mapping mouse genetic models in combination with cutting-edge imaging and sequencing technologies. This project will not only advance our understanding of the molecular mechanism of adipose plasticity, but it will also provide an ideal research training program for our HQPs.

棕色脂肪组织（BAT）和白色脂肪组织（WAT）是两种主要的哺乳动物脂肪组织，它们通过发展专门的代谢功能来适应各种环境挑战。虽然BAT通过非颤抖性产热产生热量，但WAT储存多余的能量或释放脂质以响应代谢需求，在代谢稳态中发挥重要作用。我的研究小组的总体目标是了解脂肪组织适应环境和代谢挑战的脂肪可塑性机制。长期的能量过剩通常需要从祖细胞库产生新的脂肪细胞（脂肪形成），伴随着新血管形成（血管生成）。最近的研究表明，脂肪细胞前体细胞驻留在WAT内的脂肪血管系统附近，这表明脂肪生成与血管生成的相互作用。然而，对这些动态过程如何调节的基本理解仍然不清楚。有趣的是，我们最近的数据表明，神经胶质抗原-2阳性（NG 2+）细胞有助于白色脂肪细胞和血管周细胞，参与新血管形成的细胞，这表明NG 2+细胞在脂肪形成和血管生成中的关键调节作用。因此，在目前的提案中，我们建议通过利用流式细胞术和命运定位小鼠遗传模型结合尖端成像和测序技术来表征脂肪NG 2+细胞的发育潜力及其对脂肪细胞和血管周细胞的功能贡献。本研究不仅将增进我们对脂肪可塑性的分子机制的了解，也将为我们的HQP提供一个理想的研究训练计划。