Identification of the ectoenzyme CD38 as a marker of committed preadipocytes
Identification of the ectoenzyme CD38 as a marker of committed preadipocytes
复制标题
DOI：
10.1038/ijo.2017.140
复制
发表时间：
2017-10-01
影响因子：
4.9
通讯作者：
Casteilla, L.
中科院分区：
文献类型：
--
作者：
Carriere, A.;Jeanson, Y.;Casteilla, L.
背景/目的：为了更好地了解白色脂肪组织的稳态和扩张，需要对脂肪细胞谱系进行表征。尽管一些研究集中在最不成熟的脂肪细胞祖细胞的表型上，但很少有工具可以识别定型细胞。在造血过程中，CD38 胞外酶主要用于描述干细胞谱系定型的各个阶段。我们假设该标记物可用于鉴定定型前脂肪细胞。方法：使用补充策略，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/6 J 小鼠的不同脂肪垫中分离出的小鼠脂肪祖细胞的原代培养物，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。结果：我们在此证明CD45(-)CD31(-)CD34(+)脂肪祖细胞亚群表达细胞表面蛋白CD38。使用细胞分选方法，我们发现天然CD45(-)CD31(-)CD34(+) CD38(+) (CD38(+))脂肪细胞表达的CD34 mRNA和蛋白质水平较低，而脂肪形成基因如Pparg、aP2、Lpl和Cd36的水平高于CD45(-)CD31(-)CD3(4+) CD38(-) (CD38(-)) 人口。通过BrdU掺入和集落形成单位测定评估，培养时CD38(+)细胞显示出增殖潜力降低，并且脂肪形成潜力更大。在体外，CD38 mRNA和蛋白质水平在脂肪形成过程中增加，并且CD38(-)细胞在参与脂肪形成分化程序时转化为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，这种效应在腹内脂肪中比在皮下脂肪中更明显，表明内脏库中脂肪细胞的定型率更高。 结论：总而言之，这些数据表明 CD38 代表了一种新的标记物，可将定型前脂肪细胞识别为 CD45(-)CD31(-)CD34(低)CD38(+)细胞。
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.METHODS: 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.RESULTS: 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(-)CD3(4+) 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.CONCLUSIONS: Together, these data demonstrate that CD38 represents a new marker that identifies committed preadipocytes as CD45(-)CD31(-)CD34(low) CD38(+) cells.