Single cell transcriptomics suggest that human adipocyte progenitor cells constitute a homogeneous cell population

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0701-4) contains supplementary material, which is available to authorized users.

Transforming Growth Factor-β3 Regulates Adipocyte Number in Subcutaneous White Adipose Tissue

“…Further analyses in the same dataset demonstrated that TGFB2 and -3 were most highly expressed in progenitor cells, while TGFB1 was particularly prominent in leukocytes ( Figure S1H). Data at the single-cell level (Acosta et al, 2017) confirmed an enrichment of TGFB3 in human adipocyte precursor cells ( Figure S1I).…”

“…Analyses of mRNA expression in intact or fractionated human sWAT revealed that the corresponding GF genes were primarily expressed in the SVF and only to a limited degree in mature adipocytes ( Figure S1A). Furthermore, microarray data from fractionated SVFs (Acosta et al, 2017) showed that all GFs were primarily expressed in the adipocyte progenitor (CD45 À / CD34 + /CD31 À ) cell fraction (graphs not shown). These findings were confirmed at the protein level for four of the factors.…”

Body fat mass and distribution as predictors of metabolic outcome and weight loss after Roux-en-Y gastric bypass

“…The primary source of CCL18 is M2 macrophages, but WAT release of CCL18 was highly correlated to classic proinflammatory cytokines as well. This questions the traditional division of macrophages into M1 and M2 phenotype, and rather supports more lately notions of intermediate macrophage states 157 , including metabolically activated macrophages in obesity 111 . CCL18 is known to be involved in development of pulmonary fibrosis 158 , and we hypothesized that potential metabolic effects in adipose tissue may be mediated by development of fibrosis, i.e.…”

Mapping of biguanide transporters in human fat cells and their impact on lipolysis

“…Quantitative PCR for each cDNA was conducted with Taqman probes using iTaq Universal Probe Supermix (BioRad, Hercules, CA). Microarray data of different resident cells in human subcutaneous adipose tissue were generated as described [23]. …”

“…Microarray data of different resident cells in human subcutaneous adipose tissue were generated as described. 23…”