Single-cell sequencing of human white adipose tissue identifies new cell states in health and obesity

SUMMARYWhite adipose tissue (WAT) is a dynamic tissue, which responds to environmental stimuli and dietary cues by changing its morphology and metabolic capacity. The ability of WAT to undergo a beige remodeling has become an appealing strategy to combat obesity and its related metabolic complications. Within the cell mixture that constitutes the stromal vascular fraction (SVF), WAT beiging is initiated through expansion and differentiation of adipocytes progenitor cells, however, the extent of the SVF cellular changes is still poorly understood. Additionally, direct beta 3 adrenergic receptor (Adrb3) stimulation has been extensively used to mimic physiological cold- induced beiging, yet it is still unknown whether Adrb3 activation induces the same WAT remodeling as cold exposure. Here, by using single cell RNA sequencing, we provide a comprehensive atlas of the cellular dynamics during beige remodeling within white adipose tissue. We reveal drastic changes both in the overall cellular composition and transcriptional states of individual cell subtypes between Adrb3- and cold-induced beiging. Moreover, we demonstrate that cold exposure induces a myeloid to lymphoid shift of the immune compartment compared to Adrb3 activation. Further analysis, showed that Adrb3 stimulation leads to activation of the interferon/Stat1 pathways favoring infiltration of myeloid immune cells, while repression of this pathway by cold promotes lymphoid immune cells recruitment. These findings provide new insight into the cellular dynamics during WAT beige remodeling and could ultimately lead to novel strategies to identify translationally-relevant drug targets to counteract obesity and T2D.

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Single-Cell Proteomics Reveals the Defined Heterogeneity of Resident Macrophages in White Adipose Tissue

Frontiers in Immunology ◽

10.3389/fimmu.2021.719979 ◽

2021 ◽

Vol 12 ◽

Author(s):

Inês Félix ◽

Heli Jokela ◽

Joonas Karhula ◽

Noora Kotaja ◽

Eriika Savontaus ◽

...

Keyword(s):

Adipose Tissue ◽

Single Cell ◽

White Adipose Tissue ◽

Antigen Processing ◽

Dietary Intervention ◽

Cell Mass ◽

Genetic Lineage ◽

Developmental Origin ◽

Mhc Ii ◽

Macrophage Subpopulations

Adipose tissue macrophages (ATMs) regulate homeostasis and contribute to the metabolically harmful chronic inflammation in obese individuals. While evident heterogeneity of resident ATMs has been described previously, their phenotype, developmental origin, and functionality remain inconsistent. We analyzed white adipose tissue (WAT) during homeostasis and diet interventions using comprehensive and unbiased single-cell mass cytometry and genetic lineage tracking models. We now provide a uniform definition of individual subsets of resident ATMs. We show that in lean mice, WAT co-harbors eight kinetically evolving CD206+ macrophage subpopulations (defined by TIM4, CD163, and MHC II) and two CD206– macrophage subpopulations. TIM4–CD163+, TIM4–CD163– and CD206– macrophage populations are largely bone marrow-derived, while the proliferating TIM4+CD163+ subpopulation is of embryonic origin. All macrophage subtypes are active in phagocytosis, endocytosis, and antigen processing in vitro, whereas TIM4+CD163+ cells are superior in scavenging in vivo. A high-fat diet induces massive infiltration of CD206– macrophages and selective down-regulation of MHC II on TIM4+ macrophages. These changes are reversed by dietary intervention. Thus, the developmental origin and environment jointly regulate the functional malleability of resident ATMs.

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Single cell functional genomics reveals plasticity of subcutaneous white adipose tissue (WAT) during early postnatal development

Molecular Metabolism ◽

10.1016/j.molmet.2021.101307 ◽

2021 ◽

pp. 101307

Author(s):

Elizabeth A. Rondini ◽

Vanesa D. Ramseyer ◽

Rayanne B. Burl ◽

Roger Pique-Regi ◽

James G. Granneman

Keyword(s):

Adipose Tissue ◽

Functional Genomics ◽

Single Cell ◽

Postnatal Development ◽

White Adipose Tissue ◽

Early Postnatal Development ◽

Subcutaneous White Adipose Tissue

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A single cell atlas of human and mouse white adipose tissue

10.1101/2021.11.09.466968 ◽

2021 ◽

Author(s):

Margo P Emont ◽

Christopher Jacobs ◽

Adam L Essene ◽

Deepti Pant ◽

Danielle Tenen ◽

...

Keyword(s):

Adipose Tissue ◽

Single Cell ◽

White Adipose Tissue ◽

Energy Homeostasis ◽

Cell Types ◽

Pressure Control ◽

Specific Cell ◽

Nutritional Conditions ◽

Increased Risk ◽

Stem And Progenitor Cells

White adipose tissue (WAT), once regarded as morphologically and functionally bland, is now recognized to be dynamic, plastic, heterogenous, and involved in a wide array of biological processes including energy homeostasis, glucose and lipid handling, blood pressure control, and host defense. High fat feeding and other metabolic stressors cause dramatic changes in adipose morphology, physiology, and cellular composition1, and alterations in adiposity are associated with insulin resistance, dyslipidemia, and type 2 diabetes (T2D). Here, we provide detailed cellular atlases of human and murine subcutaneous and visceral white fat at single cell resolution across a range of body weight. We identify subpopulations of adipocytes, adipose stem and progenitor cells (ASPCs), vascular, and immune cells and demonstrate commonalities and differences across species and dietary conditions. We link specific cell types to increased risk of metabolic disease, and we provide an initial blueprint for a comprehensive set of interactions between individual cell types in the adipose niche in leanness and obesity. These data comprise an extensive resource for the exploration of genes, traits, and cell types in the function of WAT across species, depots, and nutritional conditions.

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