利用单细胞表达谱技术解析β3 肾上腺素能受体激活诱导的脂肪生成。
Deconstructing Adipogenesis Induced by β3-Adrenergic Receptor Activation with Single-Cell Expression Profiling.
机构信息
Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA; Center for Integrative Metabolic and Endocrine Research, Wayne State University, Detroit, MI, USA.
Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA.
出版信息
Cell Metab. 2018 Aug 7;28(2):300-309.e4. doi: 10.1016/j.cmet.2018.05.025. Epub 2018 Jun 21.
Recruitment of brown/beige adipocytes (BAs) in white adipose tissue (WAT) involves proliferation and differentiation of adipocyte stem cells (ASCs) in concert with close interactions with resident immune cells. To deconvolve stromal cell heterogeneity in a comprehensive and unbiased fashion, we performed single-cell RNA sequencing (scRNA-seq) of >33,000 stromal/vascular cells from epididymal WAT (eWAT) and inguinal WAT (iWAT) under control conditions and during β3-adrenergic receptor (ADRB3) activation. scRNA-seq identified distinct ASC subpopulations in eWAT and iWAT that appeared to be differentially poised to enter the adipogenic pathway. ADRB3 activation triggered the dramatic appearance of proliferating ASCs in eWAT, whose differentiation into BAs could be inferred from a single time point. scRNA-seq identified various immune cell types in eWAT, including a proliferating macrophage subpopulation that occupies adipogenic niches. These results demonstrate the power of scRNA-seq to deconstruct adipogenic niches and suggest novel functional interactions among resident stromal cell subpopulations.
募集棕色/米色脂肪细胞（BAs）在白色脂肪组织（WAT）中涉及脂肪干细胞（ASCs）的增殖和分化，同时与驻留免疫细胞密切相互作用。为了全面且无偏地解析基质细胞异质性，我们对附睾 WAT（eWAT）和腹股沟 WAT（iWAT）在对照条件下和β3-肾上腺素能受体（ADRB3）激活期间的>33,000 个基质/血管细胞进行了单细胞 RNA 测序（scRNA-seq）。scRNA-seq 在 eWAT 和 iWAT 中鉴定出不同的 ASC 亚群，这些亚群似乎在进入脂肪生成途径方面具有不同的潜能。ADRB3 激活触发了 eWAT 中增殖性 ASC 的明显出现，从单个时间点可以推断出它们分化为 BAs。scRNA-seq 在 eWAT 中鉴定出各种免疫细胞类型，包括占据脂肪生成龛的增殖巨噬细胞亚群。这些结果表明 scRNA-seq 具有解构脂肪生成龛的能力，并提示驻留基质细胞亚群之间存在新的功能相互作用。
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