Robust single-nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesity.

IF 6.4 1区 生物学 Q1 BIOLOGY
eLife Pub Date : 2025-01-13 DOI:10.7554/eLife.97981
Jisun So, Olivia Strobel, Jamie Wann, Kyungchan Kim, Avishek Paul, Dominic J Acri, Luke C Dabin, Jungsu Kim, Gang Peng, Hyun Cheol Roh
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引用次数: 0

Abstract

Single-nucleus RNA sequencing (snRNA-seq), an alternative to single-cell RNA sequencing (scRNA-seq), encounters technical challenges in obtaining high-quality nuclei and RNA, persistently hindering its applications. Here, we present a robust technique for isolating nuclei across various tissue types, remarkably enhancing snRNA-seq data quality. Employing this approach, we comprehensively characterize the depot-dependent cellular dynamics of various cell types underlying mouse adipose tissue remodeling during obesity. By integrating bulk nuclear RNA-seq from adipocyte nuclei of different sizes, we identify distinct adipocyte subpopulations categorized by size and functionality. These subpopulations follow two divergent trajectories, adaptive and pathological, with their prevalence varying by depot. Specifically, we identify a key molecular feature of dysfunctional hypertrophic adipocytes, a global shutdown in gene expression, along with elevated stress and inflammatory responses. Furthermore, our differential gene expression analysis reveals distinct contributions of adipocyte subpopulations to the overall pathophysiology of adipose tissue. Our study establishes a robust snRNA-seq method, providing novel insights into the biological processes involved in adipose tissue remodeling during obesity, with broader applicability across diverse biological systems.

强大的单核RNA测序揭示了肥胖期间脂肪组织重塑中的仓库特异性细胞群体动态。
单核 RNA 测序(snRNA-seq)是单细胞 RNA 测序(scRNA-seq)的替代方法,但在获得高质量细胞核和 RNA 方面遇到了技术挑战,一直阻碍着它的应用。在这里,我们提出了一种在各种组织类型中分离细胞核的强大技术,显著提高了 snRNA-seq 数据的质量。利用这种方法,我们全面描述了肥胖过程中小鼠脂肪组织重塑所依赖的各种细胞类型的细胞动力学特征。通过整合来自不同大小脂肪细胞核的大量核 RNA-seq,我们确定了按大小和功能分类的不同脂肪细胞亚群。这些亚群遵循两种不同的轨迹,即适应性和病理性轨迹,其流行程度因脂肪库而异。具体来说,我们发现了功能失调性肥大脂肪细胞的一个关键分子特征,即基因表达的全面关闭,以及应激和炎症反应的升高。此外,我们的差异基因表达分析揭示了脂肪细胞亚群对脂肪组织整体病理生理学的不同贡献。我们的研究建立了一种稳健的 snRNA-seq 方法,为肥胖期间脂肪组织重塑所涉及的生物过程提供了新的见解,并可广泛应用于各种生物系统。
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来源期刊
eLife
eLife BIOLOGY-
CiteScore
12.90
自引率
3.90%
发文量
3122
审稿时长
17 weeks
期刊介绍: eLife is a distinguished, not-for-profit, peer-reviewed open access scientific journal that specializes in the fields of biomedical and life sciences. eLife is known for its selective publication process, which includes a variety of article types such as: Research Articles: Detailed reports of original research findings. Short Reports: Concise presentations of significant findings that do not warrant a full-length research article. Tools and Resources: Descriptions of new tools, technologies, or resources that facilitate scientific research. Research Advances: Brief reports on significant scientific advancements that have immediate implications for the field. Scientific Correspondence: Short communications that comment on or provide additional information related to published articles. Review Articles: Comprehensive overviews of a specific topic or field within the life sciences.
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