CD36 Is a Marker of Human Adipocyte Progenitors with Pronounced Adipogenic and Triglyceride Accumulation Potential

Abstract

White adipose tissue (WAT) expands in part through adipogenesis, a process involving fat cell generation and fatty acid (FA) storage into triglycerides (TGs). Several findings suggest that inter-individual and regional variations in adipogenesis are linked to metabolic complications. We aimed to identify cellular markers that define human adipocyte progenitors (APs) with pronounced adipogenic/TG storage ability. Using an unbiased single cell screen of passaged human adipose-derived stromal cells (hADSCs), we identified cell clones with similar proliferation rates but discordant capabilities to undergo adipogenic differentiation. Transcriptomic analyses prior to induction of differentiation showed that adipogenic clones displayed a significantly higher expression of CD36, encoding the scavenger receptor CD36. CD36+ hADSCs, in comparison with CD36-cells, displayed almost complete adipogenic differentiation while CD36 RNAi attenuated lipid accumulation. Similar findings were observed in primary CD45-/CD34+/CD31-APs isolated from human WAT where the subpopulation of MSCA1+/CD36+ cells displayed a significantly higher differentiation degree/TG storage capacity than MSCA1+/CD36-cells. Functional analyses in vitro and ex vivo confirmed that CD36 conferred APs an increased capacity to take up FAs thereby facilitating terminal differentiation. Among primary APs from subcutaneous femoral, abdominal and visceral human WAT, the fraction of CD36+ cells was significantly higher in depots associated with higher adipogenesis and reduced metabolic risk (i.e., femoral WAT). We conclude that CD36 marks APs with pronounced adipogenic potential, most probably by facilitating lipid uptake. This may be of value in developing human adipocyte cell clones and possibly in linking regional variations in adipogenesis to metabolic phenotype. Stem Cells 2017;35:1799-1814.

Lineage Identity and Location within the Dermis Determine the Function of Papillary and Reticular Fibroblasts in Human Skin

“…Accordingly, proliferation rates of murine fibroblasts are not only determined by their age and fibroblast lineage identity but also by the dermal composition (Lichtenberger et al, 2016).Thus, functional heterogeneity of distinct fibroblast subsets is defined by both their identity and microenvironment. For example, CD36 expression is higher in the lower dermis where adipogenesis occurs, which is coherent with its reported function (Gao et al, 2017a(Gao et al, , 2017b. Dermal microvascular endothelial cells also display heterogeneous CD36 expression depending on their localization within the dermis (Petzelbauer et al, 1993).…”

“…FAP þ CD90 þ also expressed high levels of COL11A1 and FMO1 (Figure 2e, and see Supplementary Figure S1g). Both FAP e CD90 þ and FAP þ CD90 þ fibroblasts displayed high expression levels of CD36 and PPARg, both of which are involved in fatty acid metabolism and adipogenesis (Gao et al, 2017a(Gao et al, , 2017bSiersbaek et al, 2010). These findings indicate that while FAP þ CD90 e cells represent papillary fibroblasts, FAP e CD90 þ cells depict reticular fibroblasts.…”

Ex Vivo Human Adipose Tissue Derived Mesenchymal Stromal Cells (ASC) Are a Heterogeneous Population That Demonstrate Rapid Culture-Induced Changes

“…down the osteogenic and chondrogenic mesenchymal lineages) or indeed their therapeutic potential, remains to be explored. CD271 expression has previously been associated with enhanced activity in ASC differentiation assays (Quirici et al, 2010;Barilani et al, 2018;Kohli et al, 2019) and CD36 has been associated with enhanced adipogenic potential (Gao et al, 2017). However, to our knowledge expression of podoplanin, a marker that is used to define lymphatic endothelial cells, has not been reported previously on human uncultured, ex vivo ASC.…”

Developmental and functional heterogeneity of white adipocytes within a single fat depot

“…While much attention has been paid to identifying differences between white, brown, and brite/beige adipocytes, there is growing evidence that there is functional heterogeneity among white adipocytes themselves. Thus, studies have shown that individual white adipocytes within a single depot may differ in insulin-stimulated glucose uptake, maximal lipogenic rate, response to catecholamines, and uptake of free fatty acids (Salans & Dougherty, 1971;Gliemann & Vinten, 1974;Seydoux et al, 1996;Varlamov et al, 2015;Gao et al, 2017). Indeed, lineage tracing analyses have begun to uncover the differential developmental origins of adipocytes even within single fat depots (Chau et al, 2014;Sanchez-Gurmaches & Guertin, 2014).…”