Parallel Lineage-Tracing Studies Establish Fibroblasts as the Prevailing In Vivo Adipocyte Progenitor
Parallel Lineage-Tracing Studies Establish Fibroblasts as the Prevailing In Vivo Adipocyte Progenitor
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DOI：
10.1016/j.celrep.2019.12.046
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发表时间：
2020-01-14
期刊：
影响因子：
8.8
通讯作者：
Guimaraes-Camboa, Nuno
中科院分区：
文献类型：
--
作者：
Cattaneo, Paola;Mukherjee, Debanjan;Guimaraes-Camboa, Nuno
尽管数十年的研究表明，体内脂肪细胞祖细胞存在于血管龛内，但这种祖细胞的确切性质仍然存在争议，因为不同的研究将成脂特性归因于多种血管细胞类型。使用Cre重组酶标记不同的血管谱系，我们进行平行谱系示踪实验，以评估其对从头脂肪形成的贡献程度。虽然我们偶尔检测到脂肪细胞的谱系跟踪内皮或壁重组酶，这些都是罕见的事件。另一方面，血小板衍生生长因子受体α（PDGFR α）表达的外膜或包膜成纤维细胞在所有测试的贮库和实验环境中对脂肪细胞有显著贡献。我们的数据还表明，成纤维细胞在分化为成熟的白色脂肪细胞之前转变为中间米色脂肪细胞表型。这些观察结果以及组织学分析揭示脂肪组织成纤维细胞表达壁细胞标记物PDGFR β，协调了一个极具争议的领域，对多种人类疾病（包括肥胖症大流行）产生了影响。
Despite decades of studies suggesting that the in vivo adipocyte progenitor resides within the vascular niche, the exact nature of this progenitor remains controversial because distinct studies have attributed adipogenic properties to multiple vascular cell types. Using Cre recombinases labeling distinct vascular lineages, we conduct parallel lineage tracing experiments to assess their degree of contribution to de novo adipogenesis. Although we detect occasional adipocytes that were lineage traced by endothelial or mural recombinases, these are rare events. On the other hand, platelet-derived growth factor receptor alpha (PDGFR alpha)-expressing adventitial or capsular fibroblasts make a significant contribution to adipocytes in all depots and experimental settings tested. Our data also suggest that fibroblasts transition to an intermediate beige adipocyte phenotype prior to differentiating to a mature white adipocyte. These observations, together with histological analyses revealing that adipose tissue fibroblasts express the mural cell marker PDGFR beta, harmonize a highly controversial field with implications for multiple human diseases, including the pandemic of obesity.