Cold-Induced Reprogramming of Subcutaneous White Adipose Tissue Assessed by Single-Cell and Single-Nucleus RNA Sequencing

Adipose browning has demonstrated therapeutic potentials in several diseases. Here, by conducting transcriptomic profiling at the single-cell and single-nucleus resolution, we reconstituted the cellular atlas in mouse inguinal subcutaneous white adipose tissue (iWAT) at thermoneutrality or chronic c...

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Main Authors: Qing Liu, Qiaoyun Long, Jiayu Zhao, Wenjie Wu, Zexin Lin, Wei Sun, Ping Gu, Tuo Deng, Kerry Martin Loomes, Donghai Wu, Alice P. S. Kong, Jingying Zhou, Alfred S. Cheng, Hannah Xiaoyan Hui
Format: Article
Language:English
Published: American Association for the Advancement of Science (AAAS) 2023-01-01
Series:Research
Online Access:https://spj.science.org/doi/10.34133/research.0182
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author Qing Liu
Qiaoyun Long
Jiayu Zhao
Wenjie Wu
Zexin Lin
Wei Sun
Ping Gu
Tuo Deng
Kerry Martin Loomes
Donghai Wu
Alice P. S. Kong
Jingying Zhou
Alfred S. Cheng
Hannah Xiaoyan Hui
author_facet Qing Liu
Qiaoyun Long
Jiayu Zhao
Wenjie Wu
Zexin Lin
Wei Sun
Ping Gu
Tuo Deng
Kerry Martin Loomes
Donghai Wu
Alice P. S. Kong
Jingying Zhou
Alfred S. Cheng
Hannah Xiaoyan Hui
author_sort Qing Liu
collection DOAJ
description Adipose browning has demonstrated therapeutic potentials in several diseases. Here, by conducting transcriptomic profiling at the single-cell and single-nucleus resolution, we reconstituted the cellular atlas in mouse inguinal subcutaneous white adipose tissue (iWAT) at thermoneutrality or chronic cold condition. All major nonimmune cells within the iWAT, including adipose stem and progenitor cells (ASPCs), mature adipocytes, endothelial cells, Schwann cells, and smooth muscle cells, were recovered, allowing us to uncover an overall and detailed blueprint for transcriptomes and intercellular cross-talks and the dynamics during white adipose tissue brown remodeling. Our findings also unravel the existence of subpopulations in mature adipocytes, ASPCs, and endothelial cells, as well as new insights on their interconversion and reprogramming in response to cold. The adipocyte subpopulation competent of major histocompatibility complex class II (MHCII) antigen presentation is potentiated. Furthermore, a subcluster of ASPC with CD74 expression was identified as the precursor of this MHCII+ adipocyte. Beige adipocytes are transdifferented from preexisting lipid generating adipocytes, which exhibit developmental trajectory from de novo differentiation of amphiregulin cells (Aregs). Two distinct immune-like endothelial subpopulations are present in iWAT and are responsive to cold. Our data reveal fundamental changes during cold-evoked adipose browning.
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spelling doaj.art-66ed6c58dd9e4227b2b8c05b539e6a792024-04-03T09:37:15ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742023-01-01610.34133/research.0182Cold-Induced Reprogramming of Subcutaneous White Adipose Tissue Assessed by Single-Cell and Single-Nucleus RNA SequencingQing Liu0Qiaoyun Long1Jiayu Zhao2Wenjie Wu3Zexin Lin4Wei Sun5Ping Gu6Tuo Deng7Kerry Martin Loomes8Donghai Wu9Alice P. S. Kong10Jingying Zhou11Alfred S. Cheng12Hannah Xiaoyan Hui13School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, China.School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.Department of Endocrinology, Jinling Hospital, Nanjing University, School of Medicine, Nanjing, China.National Clinical Research Center for Metabolic Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.School of Biological Sciences and Maurice Wilkins Centre, University of Auckland, Auckland, New Zealand.Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.Adipose browning has demonstrated therapeutic potentials in several diseases. Here, by conducting transcriptomic profiling at the single-cell and single-nucleus resolution, we reconstituted the cellular atlas in mouse inguinal subcutaneous white adipose tissue (iWAT) at thermoneutrality or chronic cold condition. All major nonimmune cells within the iWAT, including adipose stem and progenitor cells (ASPCs), mature adipocytes, endothelial cells, Schwann cells, and smooth muscle cells, were recovered, allowing us to uncover an overall and detailed blueprint for transcriptomes and intercellular cross-talks and the dynamics during white adipose tissue brown remodeling. Our findings also unravel the existence of subpopulations in mature adipocytes, ASPCs, and endothelial cells, as well as new insights on their interconversion and reprogramming in response to cold. The adipocyte subpopulation competent of major histocompatibility complex class II (MHCII) antigen presentation is potentiated. Furthermore, a subcluster of ASPC with CD74 expression was identified as the precursor of this MHCII+ adipocyte. Beige adipocytes are transdifferented from preexisting lipid generating adipocytes, which exhibit developmental trajectory from de novo differentiation of amphiregulin cells (Aregs). Two distinct immune-like endothelial subpopulations are present in iWAT and are responsive to cold. Our data reveal fundamental changes during cold-evoked adipose browning.https://spj.science.org/doi/10.34133/research.0182
spellingShingle Qing Liu
Qiaoyun Long
Jiayu Zhao
Wenjie Wu
Zexin Lin
Wei Sun
Ping Gu
Tuo Deng
Kerry Martin Loomes
Donghai Wu
Alice P. S. Kong
Jingying Zhou
Alfred S. Cheng
Hannah Xiaoyan Hui
Cold-Induced Reprogramming of Subcutaneous White Adipose Tissue Assessed by Single-Cell and Single-Nucleus RNA Sequencing
Research
title Cold-Induced Reprogramming of Subcutaneous White Adipose Tissue Assessed by Single-Cell and Single-Nucleus RNA Sequencing
title_full Cold-Induced Reprogramming of Subcutaneous White Adipose Tissue Assessed by Single-Cell and Single-Nucleus RNA Sequencing
title_fullStr Cold-Induced Reprogramming of Subcutaneous White Adipose Tissue Assessed by Single-Cell and Single-Nucleus RNA Sequencing
title_full_unstemmed Cold-Induced Reprogramming of Subcutaneous White Adipose Tissue Assessed by Single-Cell and Single-Nucleus RNA Sequencing
title_short Cold-Induced Reprogramming of Subcutaneous White Adipose Tissue Assessed by Single-Cell and Single-Nucleus RNA Sequencing
title_sort cold induced reprogramming of subcutaneous white adipose tissue assessed by single cell and single nucleus rna sequencing
url https://spj.science.org/doi/10.34133/research.0182
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