Mol. Cells 2022; 45(6): 362-364
Published online June 30, 2022
https://doi.org/10.14348/molcells.2022.0071
© The Korean Society for Molecular and Cellular Biology
Correspondence to : jyg.snu@gmail.com
This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.
Adipose tissue is a central metabolic organ for systemic energy homeostasis (Choe et al., 2016). Accumulating evidence suggests that adipose tissue regulates various biological processes such as energy storage, supply, thermogenesis, and immune modulation (Rosen and Spiegelman, 2014). Upon metabolic stimuli, adipose tissue exhibits dynamic changes in its structure and function, so-called adipose tissue remodeling, which appears to differ between fat depots (Hwang and Kim, 2019; Rosen and Spiegelman, 2014).
The recently developed single-cell RNA sequencing (scRNA-seq) has unveiled that adipose tissue consists of diverse subpopulations of immune cells and stem cells, and each of these subpopulations executes distinct biological functions (Jaitin et al., 2019; Lee et al., 2021; Nahmgoong et al., 2022). However, since mature adipocytes are too large and fragile to apply single-cell analysis, it has been difficult to investigate the entire subpopulations of adipose tissue at a single-cell level.
Using scRNA-seq and single-nucleus RNA-sequencing (snRNA-seq), Emont et al. (2022) recently provided a comprehensive white adipose tissue atlas from lean and obese humans and mice. They identified several subpopulations of adipocytes, adipose stem and progenitor cells (ASPCs), vascular, mesothelial, and immune cells. In addition, they compared visceral and subcutaneous adipose tissue (VAT and SAT, respectively), lean and obese subjects, and humans and mice. Further, they examined the cell–cell interaction and the relationship between the metabolic disease risk and subpopulations. Following are the highlights of their new findings.
1) Cell-type composition: In human adipose tissue, adipocytes and ASPCs accounted for the largest proportion (about 25%, respectively), followed by 10%-20% endothelial cells, and 10% macrophages. The rest of the population was comprised of smooth muscle cells, endothelial cells, and various immune cells such as T cells, NK cells, mast cells, and monocytes. Notably, mesothelial cells, which exist only in VAT, comprised over 30% of the VAT, and the proportion was increased in obese humans.
2) Immune cells: Macrophages (CD14+) and monocytes were the major immune cell types in adipose tissues (60% in humans and 90% in mice) followed by T cells and NK cells (CD96+) (30% in humans and 3% in mice). Furthermore, dendritic cells (FLT3+), B cells (MS4A1+), mast cells (CPA3+), and neutrophils (CSF3R+) were also identified. In human adipose tissue, hMac3 subpopulation exhibited unique features, which were found only in VAT, and the proportion was upregulated according to body mass index. hMac2 and mMac3 expressed
3) ASPCs: ASPCs have the potential to differentiate into adipocytes, which maintains adipocyte pools.
4) Adipocytes: In humans, adipocytes were classified into seven subpopulations including fat-depot-specific adipocyte subpopulations (hAD2/6 in VAT and hAd1/3/4/7 in SAT). Remarkably, hAd6 expressed thermogenic genes such as
5) Cell–cell communications and human diseases: The ligand-receptor interactions between adipocytes and vascular cells or ASPCs were potentiated in obesity. In obese humans, the expression levels of angiogenic factors JAG1 and VEGFC in adipocytes were increased, and concomitantly, the expression levels of receptors in endothelial cells were also upregulated. hAd7 proportion and hAd7-enriched gene expression were related to insulin resistance.
In conclusion, Emont et al. (2022) provided a comprehensive map of human and mouse white adipose tissue across anatomical location and body mass. In future, it would be important to elucidate the (patho)physiological roles of these subpopulations of adipocytes, ASPCs, immune, vascular, and mesothelial cells. Specifically, the characterization of heterogeneous adipocyte subpopulations would be crucial to understanding the role of adipocytes in energy homeostasis. In addition, the data provided in this study will also serve as an important resource. Several comparative analyses such as visceral-subcutaneous, lean-obese, and human-mouse would not only improve the understanding of adipose tissue but also be valuable resource data for translational research. Furthermore, since this study used both scRNA-seq and snRNA-seq, it would be helpful to understand the different features of these two techniques. Together, the adipose atlas in this study will broaden and deepen our understanding of adipose biology. The data in this study are readily available via Single Cell Portal (https://singlecell.broadinstitute.org/single_cell). Thus, it is recommended to embark on an adipose tissue expedition with this atlas.
This work was supported by the National Research Foundation, funded by the Korean government (Ministry of Science and ICT; NRF-2022R1C1C2003113).
The author has no potential conflicts of interest to disclose.
Mol. Cells 2022; 45(6): 362-364
Published online June 30, 2022 https://doi.org/10.14348/molcells.2022.0071
Copyright © The Korean Society for Molecular and Cellular Biology.
A comprehensive atlas of adipose tissue at the single-cell level
Yong Geun Jeon *
National Leader Research Initiatives Center for Adipocyte Structure and Function, Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul 08826, Korea
Correspondence to:jyg.snu@gmail.com
This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.
Adipose tissue is a central metabolic organ for systemic energy homeostasis (Choe et al., 2016). Accumulating evidence suggests that adipose tissue regulates various biological processes such as energy storage, supply, thermogenesis, and immune modulation (Rosen and Spiegelman, 2014). Upon metabolic stimuli, adipose tissue exhibits dynamic changes in its structure and function, so-called adipose tissue remodeling, which appears to differ between fat depots (Hwang and Kim, 2019; Rosen and Spiegelman, 2014).
The recently developed single-cell RNA sequencing (scRNA-seq) has unveiled that adipose tissue consists of diverse subpopulations of immune cells and stem cells, and each of these subpopulations executes distinct biological functions (Jaitin et al., 2019; Lee et al., 2021; Nahmgoong et al., 2022). However, since mature adipocytes are too large and fragile to apply single-cell analysis, it has been difficult to investigate the entire subpopulations of adipose tissue at a single-cell level.
Using scRNA-seq and single-nucleus RNA-sequencing (snRNA-seq), Emont et al. (2022) recently provided a comprehensive white adipose tissue atlas from lean and obese humans and mice. They identified several subpopulations of adipocytes, adipose stem and progenitor cells (ASPCs), vascular, mesothelial, and immune cells. In addition, they compared visceral and subcutaneous adipose tissue (VAT and SAT, respectively), lean and obese subjects, and humans and mice. Further, they examined the cell–cell interaction and the relationship between the metabolic disease risk and subpopulations. Following are the highlights of their new findings.
1) Cell-type composition: In human adipose tissue, adipocytes and ASPCs accounted for the largest proportion (about 25%, respectively), followed by 10%-20% endothelial cells, and 10% macrophages. The rest of the population was comprised of smooth muscle cells, endothelial cells, and various immune cells such as T cells, NK cells, mast cells, and monocytes. Notably, mesothelial cells, which exist only in VAT, comprised over 30% of the VAT, and the proportion was increased in obese humans.
2) Immune cells: Macrophages (CD14+) and monocytes were the major immune cell types in adipose tissues (60% in humans and 90% in mice) followed by T cells and NK cells (CD96+) (30% in humans and 3% in mice). Furthermore, dendritic cells (FLT3+), B cells (MS4A1+), mast cells (CPA3+), and neutrophils (CSF3R+) were also identified. In human adipose tissue, hMac3 subpopulation exhibited unique features, which were found only in VAT, and the proportion was upregulated according to body mass index. hMac2 and mMac3 expressed
3) ASPCs: ASPCs have the potential to differentiate into adipocytes, which maintains adipocyte pools.
4) Adipocytes: In humans, adipocytes were classified into seven subpopulations including fat-depot-specific adipocyte subpopulations (hAD2/6 in VAT and hAd1/3/4/7 in SAT). Remarkably, hAd6 expressed thermogenic genes such as
5) Cell–cell communications and human diseases: The ligand-receptor interactions between adipocytes and vascular cells or ASPCs were potentiated in obesity. In obese humans, the expression levels of angiogenic factors JAG1 and VEGFC in adipocytes were increased, and concomitantly, the expression levels of receptors in endothelial cells were also upregulated. hAd7 proportion and hAd7-enriched gene expression were related to insulin resistance.
In conclusion, Emont et al. (2022) provided a comprehensive map of human and mouse white adipose tissue across anatomical location and body mass. In future, it would be important to elucidate the (patho)physiological roles of these subpopulations of adipocytes, ASPCs, immune, vascular, and mesothelial cells. Specifically, the characterization of heterogeneous adipocyte subpopulations would be crucial to understanding the role of adipocytes in energy homeostasis. In addition, the data provided in this study will also serve as an important resource. Several comparative analyses such as visceral-subcutaneous, lean-obese, and human-mouse would not only improve the understanding of adipose tissue but also be valuable resource data for translational research. Furthermore, since this study used both scRNA-seq and snRNA-seq, it would be helpful to understand the different features of these two techniques. Together, the adipose atlas in this study will broaden and deepen our understanding of adipose biology. The data in this study are readily available via Single Cell Portal (https://singlecell.broadinstitute.org/single_cell). Thus, it is recommended to embark on an adipose tissue expedition with this atlas.
This work was supported by the National Research Foundation, funded by the Korean government (Ministry of Science and ICT; NRF-2022R1C1C2003113).
The author has no potential conflicts of interest to disclose.