STROMALab, Université de Toulouse, CNRS ERL 5311, EFS, INP-ENVT, Inserm, UPS, Toulouse, France.
Centre de Recherche de l'IUCPQ, Quebec, QC, Canada.
Int J Obes (Lond). 2017 Oct;41(10):1539-1546. doi: 10.1038/ijo.2017.140. Epub 2017 Jun 14.
BACKGROUND/OBJECTIVES: Characterisation of the adipocyte cellular lineage is required for a better understanding of white adipose tissue homoeostasis and expansion. Although several studies have focused on the phenotype of the most immature adipocyte progenitors, very few tools exist to identify committed cells. In haematopoiesis, the CD38 ectoenzyme is largely used to delineate various stages of stem cell lineage commitment. We hypothesise that this marker could be used to identify committed preadipocytes.
Complementary strategies including flow cytometry, cell-sorting approaches, immunohistochemistry and primary cultures of murine adipose progenitors isolated from different fat pads of control or high-fat diet exposed C57BL/6 J mice were used to determine the molecular expression profile, proliferative and differentiation potentials of adipose progenitors expressing the CD38 molecule.
We demonstrate here that a subpopulation of CD45 CD31 CD34 adipose progenitors express the cell surface protein CD38. Using a cell-sorting approach, we found that native CD45 CD31 CD34 CD38 (CD38) adipose cells expressed lower CD34 mRNA and protein levels and higher levels of adipogenic genes such as Pparg, aP2, Lpl and Cd36 than did the CD45 CD31 CD34 CD38 (CD38) population. When cultivated, CD38 cells displayed reduced proliferative potential, assessed by BrdU incorporation and colony-forming unit assays, and greater adipogenic potential. In vitro, both CD38 mRNA and protein levels were increased during adipogenesis and CD38 cells converted into CD38 cells when committed to the adipogenic differentiation programme. We also found that obesity development was associated with an increase in the number of CD38 adipose progenitors, this effect being more pronounced in intra-abdominal than in subcutaneous fat, suggesting a higher rate of adipocyte commitment in visceral depots.
Together, these data demonstrate that CD38 represents a new marker that identifies committed preadipocytes as CD45 CD31 CD34 CD38 cells.
背景/目的：为了更好地理解白色脂肪组织的稳态和扩张，需要对脂肪细胞谱系进行特征描述。虽然有几项研究集中在最不成熟的脂肪细胞祖细胞的表型上，但几乎没有工具可以识别已确定的细胞。在造血中，CD38 外切酶广泛用于描绘干细胞谱系确定的各个阶段。我们假设该标记物可用于鉴定已确定的前脂肪细胞。
包括流式细胞术、细胞分选方法、免疫组织化学和从对照或高脂肪饮食暴露的 C57BL/6J 小鼠的不同脂肪垫分离的鼠脂肪祖细胞的原代培养在内的互补策略，用于确定表达 CD38 分子的脂肪祖细胞的分子表达谱、增殖和分化潜力。
我们在此证明，CD45 CD31 CD34 脂肪祖细胞的一个亚群表达细胞表面蛋白 CD38。通过细胞分选方法，我们发现天然 CD45 CD31 CD34 CD38（CD38）脂肪细胞表达的 CD34 mRNA 和蛋白水平较低，而脂肪生成基因如 Pparg、aP2、Lpl 和 Cd36 的水平较高。与 CD45 CD31 CD34 CD38（CD38）群体相比。当培养时，CD38 细胞显示出较低的增殖潜力，通过 BrdU 掺入和集落形成单位测定评估，并且具有更大的成脂潜力。在体外，CD38 细胞在脂肪生成过程中 CD38 mRNA 和蛋白水平增加，当被确定为向脂肪生成分化方案时，CD38 细胞转化为 CD38 细胞。我们还发现，肥胖的发展与 CD38 脂肪祖细胞数量的增加有关，这种效应在内脏脂肪中比在皮下脂肪中更为明显，这表明内脏脂肪中脂肪细胞的确定速度更快。
总之，这些数据表明 CD38 代表了一种新的标记物，可将已确定的前脂肪细胞鉴定为 CD45 CD31 CD34 CD38 细胞。
