Robust single-nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesity
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...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2025-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/97981 |
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| _version_ | 1841542666403184640 |
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| author | Jisun So Olivia Strobel Jamie Wann Kyungchan Kim Avishek Paul Dominic J Acri Luke C Dabin Jungsu Kim Gang Peng Hyun Cheol Roh |
| author_facet | Jisun So Olivia Strobel Jamie Wann Kyungchan Kim Avishek Paul Dominic J Acri Luke C Dabin Jungsu Kim Gang Peng Hyun Cheol Roh |
| author_sort | Jisun So |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7ee12b2c33f44cb9a49b757acdf75cce |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-7ee12b2c33f44cb9a49b757acdf75cce2025-01-13T16:32:13ZengeLife Sciences Publications LtdeLife2050-084X2025-01-011310.7554/eLife.97981Robust single-nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesityJisun So0https://orcid.org/0000-0001-8146-8139Olivia Strobel1Jamie Wann2Kyungchan Kim3Avishek Paul4Dominic J Acri5Luke C Dabin6Jungsu Kim7https://orcid.org/0000-0002-6931-8581Gang Peng8Hyun Cheol Roh9https://orcid.org/0000-0002-8176-5747Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United StatesDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United StatesDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United StatesDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United StatesDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United StatesStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, United StatesStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, United StatesStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, United StatesDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, United StatesDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, United StatesSingle-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.https://elifesciences.org/articles/97981snRNA-seqadipocytesobesity |
| spellingShingle | Jisun So Olivia Strobel Jamie Wann Kyungchan Kim Avishek Paul Dominic J Acri Luke C Dabin Jungsu Kim Gang Peng Hyun Cheol Roh Robust single-nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesity eLife snRNA-seq adipocytes obesity |
| title | Robust single-nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesity |
| title_full | Robust single-nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesity |
| title_fullStr | Robust single-nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesity |
| title_full_unstemmed | Robust single-nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesity |
| title_short | Robust single-nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesity |
| title_sort | robust single nucleus rna sequencing reveals depot specific cell population dynamics in adipose tissue remodeling during obesity |
| topic | snRNA-seq adipocytes obesity |
| url | https://elifesciences.org/articles/97981 |
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