Abstract

Regulation of adipose tissue stem cells (ASCs) and adipogenesis impact the development of excess body fat-related metabolic complications. Animal studies have suggested the presence of distinct subtypes of ASCs with different differentiation properties. In addition, ASCs are becoming the biggest source of mesenchymal stem cells used in therapies, which requires deep characterization. Using unbiased single cell transcriptomics we aimed to characterize ASC populations in human subcutaneous white adipose tissue (scWAT). The transcriptomes of 574 single cells from the WAT total stroma vascular fraction (SVF) of four healthy women were analyzed by clustering and t-distributed stochastic neighbor embedding visualization. The identified cell populations were then mapped to cell types present in WAT using data from gene expression microarray profiling of flow cytometry-sorted SVF. Cells clustered into four distinct populations: three adipose tissue-resident macrophage subtypes and one large, homogeneous population of ASCs. While pseudotemporal ordering analysis indicated that the ASCs were in slightly different differentiation stages, the differences in gene expression were small and could not distinguish distinct ASC subtypes. Altogether, in healthy individuals, ASCs seem to constitute a single homogeneous cell population that cannot be subdivided by single cell transcriptomics, suggesting a common origin for human adipocytes in scWAT.

Highlights

  • White adipose tissue (WAT) dysfunction is central to the pathologies associated with overweight/obesity such as insulin resistance, type 2 diabetes, dyslipidemia, and atherosclerosis

  • Adipose tissue stem cell (ASC) are the most abundant cell type in the stroma vascular fraction (SVF) of WAT, and murine studies have suggested the presence of several ASC populations displaying different capacities to undergo adipogenesis [8, 9]

  • We identified the genes that best characterized these cell groups (Fig. 1c) and examined their expression in microarrays from FACSsorted SVF of subcutaneous white adipose tissue (scWAT) obtained from six different patients (Fig. 1d)

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Summary

Introduction

White adipose tissue (WAT) dysfunction is central to the pathologies associated with overweight/obesity such as insulin resistance, type 2 diabetes, dyslipidemia, and atherosclerosis. Given that ~ 10% of the adipocyte pool is renewed annually in adult humans, altered adipogenesis might impact on adipose tissue function [3, 4]. This notion is supported by the observation that hypertrophic WAT (few, large fat cells), in comparison to a ASCs are the most abundant cell type in the stroma vascular fraction (SVF) of WAT, and murine studies have suggested the presence of several ASC populations displaying different capacities to undergo adipogenesis [8, 9]. Acosta et al Stem Cell Research & Therapy (2017) 8:250 it is still unknown whether different populations of human ASCs are present in vivo

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