胸腺脂肪细胞的分子异质性和差异代谢特征
Molecular heterogeneity and differential metabolic signatures in thymic adipocytes.
作者
作者单位
- Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA.
- Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
摘要
中文
全身各处的脂肪细胞在生理和分子水平上各不相同。随着年龄增长，脂肪细胞在衰老的胸腺内及周围增多。然而，胸腺脂肪细胞缺乏分子特征描述。我们开发了从小鼠胸腺中分离脂肪细胞核的方法。对4-9月龄雄性和雌性小鼠进行单核多组学分析，揭示胸腺脂肪细胞具有异质性，存在两个不同的群体。一个亚群具有与米色脂肪一致的转录和染色质特征。另一个亚群类似于经典白色脂肪组织，并表达与上皮-间质转化（EMT）相关的基因。差异开放染色质分析确定了白色脂肪群体中Foxn1和HIF-1α/Arnt的结合位点，与这些细胞可能起源于胸腺上皮和/或低氧环境一致。免疫荧光证实了胸腺实质被膜下皮质区域细胞中UCP1蛋白的表达。这一资源揭示了胸腺脂肪细胞的复杂环境，并确定了探究其起源、动力学和功能意义的多种途径。
English
Adipocyte depots throughout the body are physiologically and molecularly distinct. With age, adipocytes increase in and around aged thymi. Yet thymic adipocytes lack molecular characterization. We developed methods to isolate adipocyte nuclei from mouse thymi. Single-nucleus multi-omic analysis of male and female mice aged 4-9 months reveals that thymic adipocytes are heterogeneous, with two distinct populations. One subpopulation harbors a transcription and chromatin signature consistent with beige fat. Another subpopulation resembles classic white adipose tissue and expresses genes associated with epithelial-to-mesenchymal transition (EMT). Analysis of differentially open chromatin identifies binding sites for Foxn1 and HIF-1α/Arnt in the white adipose population, consistent with a thymic epithelial and/or hypoxic origin for these cells. Immunofluorescence confirmed the expression of UCP1 protein in cells in subcapsular cortical regions of the thymic parenchyma. This resource reveals a complex milieu of thymic adipocytes and identifies multiple avenues for probing their ontogeny, dynamics, and functional significance.
分类与指标
- 研究类型
- 基础研究
- 病种
- 纵隔肿瘤
- JCR 分区
- Q1
- 影响因子
- 4.5
- 新锐分区
- 3区