Project

The role of Aregs in adipose biology and metabolism

Short Summary

The Deplancke lab has recently uncovered a novel stromal cell type «Aregs» in mouse fat / adipose tissue that actively blocks the formation of adipocytes, which has great biomedical implications given ist impact on ailments such as obesity and diabetes. Here, we will investigate to which extent these Aregs are relevant in humans and explore their dynamics in obese patients undergoing weight loss.

Goals

In this interdisciplinary project, we aim as a first goal to dissect the molecular mechanisms underlying the inhibitory properties of Aregs, striving to identify the molecular pathway(s) through which Aregs act. To do so, candidate genes selected on the basis of bulk and scRNA-seq data will be tested, notably by overexpression and knockdown assays. In a second aim, I will use cutting-edge scRNA-seq technologies to dissect the stromal composition of human adipose tissue, and specifically explore the frequency of Aregs and their dynamics in different physiological settings.

Significance

If Aregs turn out to meet preliminary expectations of being anti-adipogenic stromal cells, then we can envision using these cells or the anti-adipogenic molecules that they produce as potentially novel strategies to combat obesity or undesired fat accumulation in distinct tissues such as the bone marrow or muscle, which negatively affects health by respectively disrupting blood cell formation or proper muscle functioning.

Background

Given the worrying increase in the worldwide prevalence of obesity, studying the onset of this debilitating syndrome and its physiopathology is of great interest. One key aspect of such studies is understanding the regulatory mechanisms that mediate fat / adipose cell formation and thus adipose tissue plasticity. Surprisingly, our knowledge of the developmental origin of adipocytes that make up the bulk of fat tissue is still very limited. This in part reflects the highly heterogeneous and poorly characterized nature of the stromal vascular fraction (SVF) from which adipocytes likely arise. Using single cell transcriptomics (scRNA-seq), the Deplancke Lab (EPFL) has recently examined the composition of a fraction of mouse subcutaneous adipose-derived SVF cells that is considered to harbour adipose stem and progenitor cells (ASPCs). Ample heterogeneity was discovered among ASPCs, which were sub-classified into three populations. Interestingly, one subpopulation exhibited a remarkable capacity to inhibit in vitro and in vivo mammalian adipocyte formation, hence why these cells were termed Adipogenesis Regulators or Aregs.

Publications

Patents / Startups

Publications

Patents / Startups