Jiang Yuwei, Berry Daniel C, Tang Wei, Graff Jonathan M
Department of Developmental Biology, UT Southwestern Medical Center, Dallas, TX 75390-9133, USA.
Department of Developmental Biology, UT Southwestern Medical Center, Dallas, TX 75390-9133, USA; Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX 75390-9133, USA.
Cell Rep. 2014 Nov 6;9(3):1007-22. doi: 10.1016/j.celrep.2014.09.049. Epub 2014 Oct 23.
Adipose tissues have striking plasticity, highlighted by childhood and adult obesity. Using adipose lineage analyses, smooth muscle actin (SMA)-mural cell-fate mapping, and conditional PPARγ deletion to block adipocyte differentiation, we find two phases of adipocyte generation that emanate from two independent adipose progenitor compartments: developmental and adult. These two compartments are sequentially required for organ formation and maintenance. Although both developmental and adult progenitors are specified during the developmental period and express PPARγ, they have distinct microanatomical, functional, morphogenetic, and molecular profiles. Furthermore, the two compartments derive from different lineages; whereas adult adipose progenitors fate-map from an SMA+ mural lineage, developmental progenitors do not. Remarkably, the adult progenitor compartment appears to be specified earlier than the developmental cells and then enters the already developmentally formed adipose depots. Thus, two distinct cell compartments control adipose organ development and organ homeostasis, which may provide a discrete therapeutic target for childhood and adult obesity.
脂肪组织具有显著的可塑性，儿童期和成人肥胖症就突出体现了这一点。通过脂肪谱系分析、平滑肌肌动蛋白（SMA）-壁细胞命运图谱绘制以及条件性PPARγ缺失以阻断脂肪细胞分化，我们发现脂肪细胞生成有两个阶段，分别源自两个独立的脂肪祖细胞区室：发育性区室和成年区室。这两个区室对于器官形成和维持是依次必需的。尽管发育性和成年祖细胞均在发育阶段被指定并表达PPARγ，但它们具有不同的微观解剖学、功能、形态发生和分子特征。此外，这两个区室源自不同的谱系；成年脂肪祖细胞的命运图谱来自SMA +壁细胞谱系，而发育性祖细胞则并非如此。值得注意的是，成年祖细胞区室似乎比发育性细胞更早被指定，然后进入已经在发育过程中形成的脂肪库。因此，两个不同的细胞区室控制着脂肪器官的发育和器官稳态，这可能为儿童期和成人肥胖症提供一个独特的治疗靶点。
