FSP1-positive fibroblasts are adipogenic niche and regulate adipose homeostasis.
FSP1-positive fibroblasts are adipogenic niche and regulate adipose homeostasis.
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FSP1 阳性成纤维细胞是脂肪生成生态位并调节脂肪稳态。
DOI：
10.1371/journal.pbio.2001493
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发表时间：
2018-08
期刊：
影响因子：
9.8
通讯作者：
Ge G
中科院分区：
文献类型：
--
作者：
Zhang R;Gao Y;Zhao X;Gao M;Wu Y;Han Y;Qiao Y;Luo Z;Yang L;Chen J;Ge G
脂肪细胞祖细胞存在于由成纤维细胞、免疫细胞和内皮细胞组成的脂肪组织的基质血管部分（SVF）中。 SVF 如何调节脂肪细胞祖细胞命运决定和脂肪稳态仍有待阐明。在这里，我们报告说，SVF 中的成纤维细胞特异性蛋白 1 (FSP1)+ 成纤维细胞对于脂肪稳态至关重要。 FSP1+ 成纤维细胞缺乏成脂潜力，与 SVF 中的前脂肪细胞相邻。小鼠 FSP1+ 成纤维细胞的消融会严重减少脂肪库的脂肪含量。 FSP1+ 成纤维细胞中经典 Wnt 信号的激活会导致脂肪组织逐渐减少，并对饮食引起的肥胖产生抵抗力。 FSP1+ 成纤维细胞的改变会减少血小板衍生生长因子 (PDGF)-BB 信号传导，并导致前脂肪细胞损失。同时，PDGF-BB 信号传导减弱，通过调节基质金属蛋白酶 (MMP) 表达、细胞外基质重塑和 Yes 相关蛋白 (YAP) 信号传导，损害前脂肪细胞的成脂分化能力。因此，FSP1+成纤维细胞是维持前脂肪细胞池及其在脂肪稳态中的成脂潜力所必需的重要生态位。白色脂肪组织（WAT）主要由脂肪细胞组成，它不仅是被动的能量储存器官，也是体内主动的代谢和内分泌器官。肥胖个体中脂肪组织过多和缺乏都会产生不利的代谢后果，这一事实强调了保持适当脂肪量的重要性。为了维持脂肪细胞的数量，成人中前脂肪细胞不断更新。与任何其他成体干细胞和祖细胞一样，前脂肪细胞的细胞命运和分化能力受到高度专业化的生态位的严格调控。然而，前脂肪细胞生态位的构成以及前脂肪细胞生态位如何调节前脂肪细胞功能和脂肪稳态仍知之甚少。在这项研究中，我们发现小鼠 WAT 基质血管部分 (SVF) 中的成纤维细胞特异性蛋白 1 (FSP1)+ 成纤维细胞是前脂肪细胞的微环境。我们发现，具有异常 Wnt 信号传导的 FSP1+ 成纤维细胞无法维持前脂肪细胞库及其分化潜力，导致脂肪组织损失。我们得出的结论是，FSP1+ 成纤维细胞是前脂肪细胞的一个利基，并调节成年小鼠的脂肪组织稳态。
Adipocyte progenitors reside in the stromal vascular fraction (SVF) of adipose tissues that are composed of fibroblasts, immune cells, and endothelial cells. It remains to be elucidated how the SVF regulates adipocyte progenitor fate determination and adipose homeostasis. Here, we report that fibroblast-specific protein-1 (FSP1)+ fibroblasts in the SVF are essential to adipose homeostasis. FSP1+ fibroblasts, devoid of adipogenic potential, are adjacent to the preadipocytes in the SVF. Ablation of FSP1+ fibroblasts in mice severely diminishes fat content of adipose depots. Activation of canonical Wnt signaling in the FSP1+ fibroblasts results in gradual loss of adipose tissues and resistance to diet-induced obesity. Alterations in the FSP1+ fibroblasts reduce platelet-derived growth factor (PDGF)-BB signaling and result in the loss of preadipocytes. Reduced PDGF-BB signaling, meanwhile, impairs the adipogenic differentiation capability of preadipocytes by regulating matrix metalloproteinase (MMP) expression, extracellular matrix remodeling, and the activation of Yes-associated protein (YAP) signaling. Thus, FSP1+ fibroblasts are an important niche essential to the maintenance of the preadipocyte pool and its adipogenic potential in adipose homeostasis. White adipose tissue (WAT), which consists mostly of adipocytes, is not only a passive energy storage but also an active metabolic and endocrine organ in the body. The importance of maintaining proper adipose mass is emphasized by the fact that both adipose tissue excess—in obese individuals—and deficiency have adverse metabolic consequences. In order to maintain the number of adipocytes, there is a continuous turnover from preadipocytes in adults. Like any other adult stem cells and progenitor cells, cell fate and differentiation capability of preadipocytes are tightly regulated by a highly specialized niche. However, what constitutes the preadipocyte niche, and how the niche regulates preadipocyte function and adipose homeostasis, remain poorly known. In this study, we have identified fibroblast-specific protein-1 (FSP1)+ fibroblasts in the WAT stromal vascular fraction (SVF) of mice as the niche for preadipocytes. We show that FSP1+ fibroblasts with aberrant Wnt signaling fail to maintain the preadipocyte pool and its differentiation potential, resulting in loss of adipose tissue. We conclude that FSP1+ fibroblasts are a niche for preadipocytes and regulate adipose tissue homeostasis in adult mice.
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影响因子：
29
作者：
Jeffery E;Wing A;Holtrup B;Sebo Z;Kaplan JL;Saavedra-Peña R;Church CD;Colman L;Berry R;Rodeheffer MS
通讯作者：
Rodeheffer MS
影响因子：
64.5
作者：
Rodeheffer, Matthew S.;Birsoy, Kivanc;Friedman, Jeffrey M.
通讯作者：
Friedman, Jeffrey M.
影响因子：
21.3
作者：
通讯作者：
--
DOI：
10.1007/978-1-60761-999-4_19
发表时间：
2011-01-01
期刊：
MESENCHYMAL STEM CELL ASSAYS AND APPLICATIONS
影响因子：
--
作者：
Fink, Trine;Zachar, Vladimir
通讯作者：
Zachar, Vladimir
影响因子：
4.8
作者：
Longo, KA;Wright, WS;MacDougald, OA
通讯作者：
MacDougald, OA