ABSTRACT

Some adipocytes are produced from bone marrow hematopoietic stem cells. In vitro studies previously indicated that these bone marrow-derived adipocytes (BMDAs) were generated from adipose tissue macrophage (ATM) that lose their hematopoietic markers and acquire mesenchymal markers prior to terminal adipogenic differentiation. Here we interrogated whether this hematopoietic-to-mesenchymal transition drives BMDA production In vitro. We generated transgenic mice in which the lysozyme gene promoter (LysM) indelibly labeled ATM with green fluorescent protein (GFP). We discovered that adipose stroma contained a population of LysM-positive myeloid cells that simultaneously expressed hematopoietic/myeloid markers (CD45 and CD11b), and mesenchymal markers (CD29, PDGFRa and Sca-1) typically found on conventional adipocyte progenitors. These cells were capable of adipogenic differentiation In vitro and In vitro, while other stromal populations deficient in PDGFRa and Sca-1 were non-adipogenic. BMDAs and conventional adipocytes expressed common fat cell markers but exhibited little or no expression of hematopoietic and mesenchymal progenitor cell markers. The data indicate that BMDAs are produced from ATM simultaneously expressing hematopoietic and mesenchymal markers rather than via a stepwise hematopoietic-to-mesenchymal transition. Because BMDA production is stimulated by high fat feeding, their production from hematopoietic progenitors may maintain adipocyte production when conventional adipocyte precursors are diminished.

摘要

一些脂肪细胞是由骨髓造血干细胞产生的。先前的体外研究表明，这些骨髓来源的脂肪细胞 (BMDA) 是由脂肪组织巨噬细胞 (ATM) 产生的，这些巨噬细胞在终末脂肪形成分化之前失去了造血标志物并获得了间充质标志物。在这里，我们询问了这种造血-间质转化是否会在体外驱动 BMDA 的产生. 我们生成了转基因小鼠，其中溶菌酶基因启动子 (LysM) 用绿色荧光蛋白 (GFP) 对 ATM 进行了不可磨灭的标记。我们发现脂肪基质含有一组 LysM 阳性骨髓细胞，这些细胞同时表达造血/骨髓标志物（CD45 和 CD11b），以及通常在传统脂肪细胞祖细胞上发现的间充质标志物（CD29、PDGFRa 和 Sca-1）。这些细胞能够在体外和体外进行脂肪形成分化，而其他缺乏 PDGFRa 和 Sca-1 的基质群体是非脂肪形成的。BMDA 和常规脂肪细胞表达常见的脂肪细胞标志物，但很少或不表达造血和间充质祖细胞标志物。数据表明，BMDA 是由同时表达造血和间充质标志物的 ATM 产生的，而不是通过逐步的造血-间质转化。由于 BMDA 的产生受到高脂肪喂养的刺激，因此当常规脂肪细胞前体减少时，造血祖细胞产生的 BMDA 可以维持脂肪细胞的产生。