Nahmgoong Hahn, Jeon Yong Geun, Park Eun Seo, Choi Yoon Ha, Han Sang Mun, Park Jeu, Ji Yul, Sohn Jee Hyung, Han Ji Seul, Kim Ye Young, Hwang Injae, Lee Yun Kyung, Huh Jin Young, Choe Sung Sik, Oh Tae Jung, Choi Sung Hee, Kim Jong Kyoung, Kim Jae Bum
National Creative Research Initiatives Center for Adipocyte Structure and Function, Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea.
Department of New Biology, DGIST, Daegu 42988, Republic of Korea.
Cell Metab. 2022 Mar 1;34(3):458-472.e6. doi: 10.1016/j.cmet.2021.11.014. Epub 2022 Jan 11.
In mammals, white adipose tissues are largely divided into visceral epididymal adipose tissue (EAT) and subcutaneous inguinal adipose tissue (IAT) with distinct metabolic properties. Although emerging evidence suggests that subpopulations of adipose stem cells (ASCs) would be important to explain fat depot differences, ASCs of two fat depots have not been comparatively investigated. Here, we characterized heterogeneous ASCs and examined the effects of intrinsic and tissue micro-environmental factors on distinct ASC features. We demonstrated that ASC subpopulations in EAT and IAT exhibited different molecular features with three adipogenic stages. ASC transplantation experiments revealed that intrinsic ASC features primarily determined their adipogenic potential. Upon obesogenic stimuli, EAT-specific SDC1 ASCs promoted fibrotic remodeling, whereas IAT-specific CXCL14 ASCs suppressed macrophage infiltration. Moreover, IAT-specific BST2 ASCs exhibited a high potential to become beige adipocytes. Collectively, our data broaden the understanding of ASCs with new insights into the origin of white fat depot differences.
在哺乳动物中,白色脂肪组织主要分为具有不同代谢特性的内脏附睾脂肪组织(EAT)和皮下腹股沟脂肪组织(IAT)。尽管新出现的证据表明脂肪干细胞(ASC)亚群对于解释脂肪储存差异很重要,但尚未对两个脂肪储存部位的ASC进行比较研究。在此,我们对异质性ASC进行了表征,并研究了内在因素和组织微环境因素对不同ASC特征的影响。我们证明,EAT和IAT中的ASC亚群在三个成脂阶段表现出不同的分子特征。ASC移植实验表明,内在的ASC特征主要决定了它们的成脂潜力。在致肥胖刺激下,EAT特异性SDC1 ASC促进纤维化重塑,而IAT特异性CXCL14 ASC抑制巨噬细胞浸润。此外,IAT特异性BST2 ASC具有很高的成为米色脂肪细胞的潜力。总的来说,我们的数据拓宽了对ASC的理解,为白色脂肪储存差异的起源提供了新的见解。