Fat depot-specific gene signature and ECM remodeling of Sca1(high) adipose-derived stem cells.

Fat depot-specific gene signature and ECM remodeling of Sca1(high) adipose-derived stem cells.
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DOI:
10.1016/j.matbio.2014.03.005
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发表时间:
2014-06
期刊:
影响因子:
6.9
通讯作者:
Chun, Tae-Hwa
Chun, Tae-Hwa
中科院分区:
生物学1区
文献类型:
--
作者:
Tokunaga, Masakuni;Inoue, Mayumi;Jiang, Yibin;Barnes, Richard H., II;Buchner, David A.;Chun, Tae-Hwa

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干细胞抗原-1(Sca 1或Ly 6A/E)是一种细胞表面标志物,广泛表达于间充质干细胞,包括脂肪源性干细胞(ASC)。我们假设Sca 1high ASCs的脂肪库特异性基因特征可能在定义脂肪组织功能和细胞外基质(ECM)重塑中发挥主要作用。在此,我们旨在表征从皮下(腹股沟)和内脏(附睾)脂肪组织分离的Sca 1high ASCs的独特基因特征和ECM重塑。Sca 1highASCs存在于脂肪组织的外膜和血管周围区域。用磁激活细胞分选(MACS)纯化的Sca 1high ASC表现出树突状或圆形形状,具有较高的细胞因子和趋化因子表达(例如,IL 6,Cxcl 1)和葡萄糖转运蛋白(Glut 1)的低表达。皮下和内脏脂肪来源的Sca 1high ASCs在粘附和ECM分子的基因表达方面特别不同。虽然两组间主要膜型胶原酶(MMP 14)的表达相当,但分泌型胶原酶(MMP 8和MMP 13)的表达在内脏Sca 1高ASC中高于皮下ASC。皮下Sca 1high ASCs观察到一致的、缓慢的但局灶性的MMP依赖性胶原溶解,而内脏Sca 1high ASCs以MMP依赖性和非依赖性方式观察到快速和大量的胶原溶解。这些结果表明,脂肪储存库特异性基因签名的ASCs可能有助于不同的ECM重塑和脂肪功能的模式在不同的脂肪储存库。
Stem Cell Antigen-1 (Sca1 or Ly6A/E) is a cell surface marker that is widely expressed in mesenchymal stem cells, including adipose-derived stem cells (ASCs). We hypothesized that the fat depot-specific gene signature of Sca1high ASCs may play the major role in defining adipose tissue function and extracellular matrix (ECM) remodeling in a depot-specific manner. Herein we aimed to characterize the unique gene signature and ECM remodeling of Sca1high ASCs isolated from subcutaneous (inguinal) and visceral (epididymal) adipose tissues. Sca1high ASCs are found in the adventitia and perivascular area of adipose tissues. Sca1high ASCs purified with magnetic-activated cell sorting (MACS) demonstrate dendrite or round shape with the higher expression of cytokines and chemokines (e.g., Il6, Cxcl1) and the lower expression of a glucose transporter (Glut1). Subcutaneous and visceral fat-derived Sca1high ASCs particularly differ in the gene expressions of adhesion and ECM molecules. While the expression of the major membrane-type collagenase (MMP14) is comparable between the groups, the expressions of secreted collagenases (MMP8 and MMP13) are higher in visceral Sca1high ASCs than subcutaneous ASCs. Consistently, slow but focal MMP-dependent collagenolysis was observed with subcutaneous Sca1high ASCs, whereas rapid and bulk collagenolysis was observed with visceral Sca1high ASCs in MMP-dependent and –independent manners. These results suggest that the fat depot-specific gene signatures of ASCs may contribute to the distinct patterns of ECM remodeling and adipose function in different fat depots.
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