snRNA-seq reveals subcutaneous white adipose tissue remodeling upon return to thermoneutrality after cold stimulation
IntroductionCold stimulation induces browning of subcutaneous white adipose tissue (sWAT), making it a prime target for treating obesity and metabolic disorders. However, this remodeling is reversible: upon return to thermoneutrality (rewarming), sWAT whitens and loses its enhanced metabolic functio...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-05-01
|
| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2025.1578180/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850260471886643200 |
|---|---|
| author | Yusha Yang Yusha Yang Guanyu Zhang Ting Yi Ting Yi Shuran Yang Shuran Yang Shuai Wu Yongqiang Zhang Li Zhang Xi Li Xiuxuan Wu Xiuxuan Wu Jun Li Danfeng Yang |
| author_facet | Yusha Yang Yusha Yang Guanyu Zhang Ting Yi Ting Yi Shuran Yang Shuran Yang Shuai Wu Yongqiang Zhang Li Zhang Xi Li Xiuxuan Wu Xiuxuan Wu Jun Li Danfeng Yang |
| author_sort | Yusha Yang |
| collection | DOAJ |
| description | IntroductionCold stimulation induces browning of subcutaneous white adipose tissue (sWAT), making it a prime target for treating obesity and metabolic disorders. However, this remodeling is reversible: upon return to thermoneutrality (rewarming), sWAT whitens and loses its enhanced metabolic functions. Given the limited understanding of the microscopic dynamic changes and underlying mechanisms during this process, we established a temporally dynamic mouse model spanning the entire period from cold stimulation to the return to thermoneutrality, with inguinal sWAT (iWAT) selected as the study subject.MethodsBased on preliminary data demonstrating stabilization in iWAT histology, expression levels of key thermogenic proteins, and the bulk transcriptome, we selected the two-week time point after the return to thermoneutrality for detailed analysis. Subsequently, we employed single-nucleus RNA sequencing (snRNA-seq) to comprehensively characterize iWAT cellular dynamics during cold stimulation and the subsequent two-week period after the return to thermoneutrality.ResultsOur findings revealed that while iWAT phenotypically reverts to a white state after 2 weeks of rewarming, as evidenced by structural, functional, and bulk transcriptomic characteristics, significant cold-induced molecular and cellular signatures persist. Specifically, we observed altered differentiation trajectories in both adipose stem and progenitor cells (ASPCs) and adipocytes, suggesting dedifferentiation and reprogramming tendencies. Furthermore, the ANGPTL signaling pathway, activated in thermogenic adipocyte subpopulation A3 during cold stimulation, remained active and influenced cell-cell communication even after the loss of thermogenic capacity.Discussionhese findings provide novel insights into elucidating the complex cellular and molecular mechanisms underlying the temperature-dependent plasticity of iWAT, and suggest that the ANGPTL signaling pathway may play a potential role in maintaining the white phenotype of iWAT after withdrawal from cold stimulation. |
| format | Article |
| id | doaj-art-6d3d59fe2d5b48209371595fba64b8eb |
| institution | OA Journals |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-6d3d59fe2d5b48209371595fba64b8eb2025-08-20T01:55:38ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-05-011310.3389/fcell.2025.15781801578180snRNA-seq reveals subcutaneous white adipose tissue remodeling upon return to thermoneutrality after cold stimulationYusha Yang0Yusha Yang1Guanyu Zhang2Ting Yi3Ting Yi4Shuran Yang5Shuran Yang6Shuai Wu7Yongqiang Zhang8Li Zhang9Xi Li10Xiuxuan Wu11Xiuxuan Wu12Jun Li13Danfeng Yang14School of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, ChinaAcademy of Military Medical Sciences, Academy of Military Sciences, Tianjin, ChinaAcademy of Military Medical Sciences, Academy of Military Sciences, Tianjin, ChinaSchool of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, ChinaAcademy of Military Medical Sciences, Academy of Military Sciences, Tianjin, ChinaAcademy of Military Medical Sciences, Academy of Military Sciences, Tianjin, ChinaSchool of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaAcademy of Military Medical Sciences, Academy of Military Sciences, Tianjin, ChinaAcademy of Military Medical Sciences, Academy of Military Sciences, Tianjin, ChinaAcademy of Military Medical Sciences, Academy of Military Sciences, Tianjin, ChinaAcademy of Military Medical Sciences, Academy of Military Sciences, Tianjin, ChinaSchool of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, ChinaAcademy of Military Medical Sciences, Academy of Military Sciences, Tianjin, ChinaSchool of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, ChinaAcademy of Military Medical Sciences, Academy of Military Sciences, Tianjin, ChinaIntroductionCold stimulation induces browning of subcutaneous white adipose tissue (sWAT), making it a prime target for treating obesity and metabolic disorders. However, this remodeling is reversible: upon return to thermoneutrality (rewarming), sWAT whitens and loses its enhanced metabolic functions. Given the limited understanding of the microscopic dynamic changes and underlying mechanisms during this process, we established a temporally dynamic mouse model spanning the entire period from cold stimulation to the return to thermoneutrality, with inguinal sWAT (iWAT) selected as the study subject.MethodsBased on preliminary data demonstrating stabilization in iWAT histology, expression levels of key thermogenic proteins, and the bulk transcriptome, we selected the two-week time point after the return to thermoneutrality for detailed analysis. Subsequently, we employed single-nucleus RNA sequencing (snRNA-seq) to comprehensively characterize iWAT cellular dynamics during cold stimulation and the subsequent two-week period after the return to thermoneutrality.ResultsOur findings revealed that while iWAT phenotypically reverts to a white state after 2 weeks of rewarming, as evidenced by structural, functional, and bulk transcriptomic characteristics, significant cold-induced molecular and cellular signatures persist. Specifically, we observed altered differentiation trajectories in both adipose stem and progenitor cells (ASPCs) and adipocytes, suggesting dedifferentiation and reprogramming tendencies. Furthermore, the ANGPTL signaling pathway, activated in thermogenic adipocyte subpopulation A3 during cold stimulation, remained active and influenced cell-cell communication even after the loss of thermogenic capacity.Discussionhese findings provide novel insights into elucidating the complex cellular and molecular mechanisms underlying the temperature-dependent plasticity of iWAT, and suggest that the ANGPTL signaling pathway may play a potential role in maintaining the white phenotype of iWAT after withdrawal from cold stimulation.https://www.frontiersin.org/articles/10.3389/fcell.2025.1578180/fullsingle-nucleus RNA sequencingthermoneutralitysubcutaneous white adipose tissueplasticitycold stimulation |
| spellingShingle | Yusha Yang Yusha Yang Guanyu Zhang Ting Yi Ting Yi Shuran Yang Shuran Yang Shuai Wu Yongqiang Zhang Li Zhang Xi Li Xiuxuan Wu Xiuxuan Wu Jun Li Danfeng Yang snRNA-seq reveals subcutaneous white adipose tissue remodeling upon return to thermoneutrality after cold stimulation Frontiers in Cell and Developmental Biology single-nucleus RNA sequencing thermoneutrality subcutaneous white adipose tissue plasticity cold stimulation |
| title | snRNA-seq reveals subcutaneous white adipose tissue remodeling upon return to thermoneutrality after cold stimulation |
| title_full | snRNA-seq reveals subcutaneous white adipose tissue remodeling upon return to thermoneutrality after cold stimulation |
| title_fullStr | snRNA-seq reveals subcutaneous white adipose tissue remodeling upon return to thermoneutrality after cold stimulation |
| title_full_unstemmed | snRNA-seq reveals subcutaneous white adipose tissue remodeling upon return to thermoneutrality after cold stimulation |
| title_short | snRNA-seq reveals subcutaneous white adipose tissue remodeling upon return to thermoneutrality after cold stimulation |
| title_sort | snrna seq reveals subcutaneous white adipose tissue remodeling upon return to thermoneutrality after cold stimulation |
| topic | single-nucleus RNA sequencing thermoneutrality subcutaneous white adipose tissue plasticity cold stimulation |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2025.1578180/full |
| work_keys_str_mv | AT yushayang snrnaseqrevealssubcutaneouswhiteadiposetissueremodelinguponreturntothermoneutralityaftercoldstimulation AT yushayang snrnaseqrevealssubcutaneouswhiteadiposetissueremodelinguponreturntothermoneutralityaftercoldstimulation AT guanyuzhang snrnaseqrevealssubcutaneouswhiteadiposetissueremodelinguponreturntothermoneutralityaftercoldstimulation AT tingyi snrnaseqrevealssubcutaneouswhiteadiposetissueremodelinguponreturntothermoneutralityaftercoldstimulation AT tingyi snrnaseqrevealssubcutaneouswhiteadiposetissueremodelinguponreturntothermoneutralityaftercoldstimulation AT shuranyang snrnaseqrevealssubcutaneouswhiteadiposetissueremodelinguponreturntothermoneutralityaftercoldstimulation AT shuranyang snrnaseqrevealssubcutaneouswhiteadiposetissueremodelinguponreturntothermoneutralityaftercoldstimulation AT shuaiwu snrnaseqrevealssubcutaneouswhiteadiposetissueremodelinguponreturntothermoneutralityaftercoldstimulation AT yongqiangzhang snrnaseqrevealssubcutaneouswhiteadiposetissueremodelinguponreturntothermoneutralityaftercoldstimulation AT lizhang snrnaseqrevealssubcutaneouswhiteadiposetissueremodelinguponreturntothermoneutralityaftercoldstimulation AT xili snrnaseqrevealssubcutaneouswhiteadiposetissueremodelinguponreturntothermoneutralityaftercoldstimulation AT xiuxuanwu snrnaseqrevealssubcutaneouswhiteadiposetissueremodelinguponreturntothermoneutralityaftercoldstimulation AT xiuxuanwu snrnaseqrevealssubcutaneouswhiteadiposetissueremodelinguponreturntothermoneutralityaftercoldstimulation AT junli snrnaseqrevealssubcutaneouswhiteadiposetissueremodelinguponreturntothermoneutralityaftercoldstimulation AT danfengyang snrnaseqrevealssubcutaneouswhiteadiposetissueremodelinguponreturntothermoneutralityaftercoldstimulation |