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Multidimensional Single-Nuclei RNA-Seq Reconstruction of Adipose Tissue Reveals Adipocyte Plasticity Underlying Thermogenic Response

View ORCID ProfileCarlos Alberto Oliveira de Biagi Junior, View ORCID ProfileSarah Santiloni Cury, View ORCID ProfileCleidson de Pádua Alves, View ORCID ProfileNabil Rabhi, View ORCID ProfileWilson Araujo Silva Jr., View ORCID ProfileStephen R. Farmer, View ORCID ProfileRobson Francisco Carvalho, View ORCID ProfileMiguel Luiz Batista Jr.
doi: https://doi.org/10.1101/2021.02.16.431320
Carlos Alberto Oliveira de Biagi Junior
1Department of Genetics at Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
2Center for Cell-Based Therapy (CEPID/FAPESP); National Institute of Science and Technology in Stem Cell and Cell Therapy (INCTC/CNPq), Regional Blood Center of Ribeirão Preto, Ribeirão Preto, Brazil.
7Institute for Cancer Research, IPEC, Guarapuava, PR, Brazil.
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  • ORCID record for Carlos Alberto Oliveira de Biagi Junior
Sarah Santiloni Cury
3Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil.
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Cleidson de Pádua Alves
4Department of Translational Genomics, Medical Faculty, University of Cologne, Cologne, Germany
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Nabil Rabhi
5Department of Biochemistry, Boston University School of Medicine, Boston, U.S.A.
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Wilson Araujo Silva Jr.
1Department of Genetics at Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
2Center for Cell-Based Therapy (CEPID/FAPESP); National Institute of Science and Technology in Stem Cell and Cell Therapy (INCTC/CNPq), Regional Blood Center of Ribeirão Preto, Ribeirão Preto, Brazil.
7Institute for Cancer Research, IPEC, Guarapuava, PR, Brazil.
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Stephen R. Farmer
5Department of Biochemistry, Boston University School of Medicine, Boston, U.S.A.
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Robson Francisco Carvalho
3Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil.
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  • For correspondence: migueljr4@me.com robson.carvalho@unesp.br
Miguel Luiz Batista Jr.
5Department of Biochemistry, Boston University School of Medicine, Boston, U.S.A.
6Department of Integrated Biotechnology, University of Mogi das Cruzes, São Paulo, Brazil.
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  • For correspondence: migueljr4@me.com robson.carvalho@unesp.br
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Abstract

Adipose tissue has been classified based on its morphology and function as white, brown, or beige / brite. It plays an essential role as a regulator of systemic metabolism through paracrine and endocrine signals. Recently, multiple adipocyte subtypes have been revealed using RNA sequencing technology, going beyond simply defined morphology but by their cellular origin, adaptation to metabolic stress, and plasticity. Here, we performed an in-depth analysis of publicly available single-nuclei RNAseq from adipose tissue and utilized a workflow template to characterize adipocyte plasticity, heterogeneity, and secretome profiles. The reanalyzed dataset led to the identification of different subtypes of adipocytes including three subpopulations of thermogenic adipocytes and provided a characterization of distinct transcriptional profiles along the adipocyte trajectory under thermogenic challenges. This study provides a useful resource for further investigations regarding mechanisms related to adipocyte plasticity and trans-differentiation.

Highlights Multidimensional transcriptome analysis at single-nucleus resolution recovers nuclei of cell types in adipose tissue

Adaptative thermogenic response results in 3 distinct mature adipose cell types

Single-nuclei transcriptomic-based secretome analysis reveals adipose cell-type-specific genes

The in vivo trajectory of adipocyte plasticity for thermogenic response reveals sets of trans-differentiation genes

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Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵9 Co-senior author

  • ↵10 Lead author

  • Introduction session and references were updated; author affiliations updated.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted February 27, 2021.
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Multidimensional Single-Nuclei RNA-Seq Reconstruction of Adipose Tissue Reveals Adipocyte Plasticity Underlying Thermogenic Response
Carlos Alberto Oliveira de Biagi Junior, Sarah Santiloni Cury, Cleidson de Pádua Alves, Nabil Rabhi, Wilson Araujo Silva Jr., Stephen R. Farmer, Robson Francisco Carvalho, Miguel Luiz Batista Jr.
bioRxiv 2021.02.16.431320; doi: https://doi.org/10.1101/2021.02.16.431320
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Multidimensional Single-Nuclei RNA-Seq Reconstruction of Adipose Tissue Reveals Adipocyte Plasticity Underlying Thermogenic Response
Carlos Alberto Oliveira de Biagi Junior, Sarah Santiloni Cury, Cleidson de Pádua Alves, Nabil Rabhi, Wilson Araujo Silva Jr., Stephen R. Farmer, Robson Francisco Carvalho, Miguel Luiz Batista Jr.
bioRxiv 2021.02.16.431320; doi: https://doi.org/10.1101/2021.02.16.431320

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