Biology subjects

Poupel, L.

Publications and source records attributed to Poupel, L..

3 recordsLinked to original sources

bioRxiv2023

Obesity-elicited macrophages shape CD9hi progenitor fate to promote adipose tissue fibrosis and dysfunction

Obesity is a life-threatening condition characterized by a maladaptive remodeling of the visceral white adipose tissue (vWAT), including fibrosis, that drives vWAT metabolic alterations. We previously identified CD9hi adipose tissue progenitors as the main drivers of vWAT fibrosis in mice and humans. However, how their functions are controlled, especially by macrophages, remains largely unknown. We found that obesity-elicited monocyte-derived macrophages (obeMac) accumulation was considerably elevated in mice prone to obesity-induced vWAT fibrosis. Limiting obeMac build-up decreased the numbers and fibrogenic activation of CD9hi progenitors, leading to decreased vWAT fibrosis and improved glucose homeostasis. In patients with obesity, we identified macrophages similar to mouse obeMacs that were associated with accumulation of CD9hi progenitors in the vWAT and loss of glycemic control. Finally, intercellular communication analysis identified mediators produced by obeMacs that control the fibrogenic potential of CD9hi progenitors. Together, we uncovered an obeMac-CD9hi progenitors axis controlling vWAT fibrosis and dysfunction.

pathology↗

bioRxiv2023

Loss of embryonically-derived Kupffer cells during hypercholesterolemia accelerates atherosclerosis development

Hypercholesterolemia is a major risk factor for atherosclerosis and associated cardiovascular diseases. The liver plays a key role in the regulation of plasma cholesterol levels and hosts a large population of tissue-resident macrophages known as Kupffer cells (KCs). KCs are located in the hepatic sinusoids where they ensure key functions including blood immune surveillance. However, how KCs homeostasis is affected by the build-up of cholesterol-rich lipoproteins that occurs in the circulation during hypercholesterolemia remains unknown. Here, we found that embryo-derived KCs (EmKCs) accumulated large amounts of lipoprotein-derived cholesterol, in part through the scavenger receptor CD36, and massively expanded early after the induction of hypercholesterolemia. After this rapid adaptive response, EmKCs exhibited mitochondrial oxidative stress and their numbers gradually diminished while monocyte-derived KCs (MoKCs) with reduced cholesterol-loading capacities seeded the KC pool. Decreased proportion of EmKCs in the KC pool enhanced liver cholesterol content and exacerbated hypercholesterolemia, leading to accelerated atherosclerotic plaque development. Together, our data reveal that KC homeostasis is perturbed during hypercholesterolemia, which in turn alters the control of plasma cholesterol levels and increases atherosclerosis.

pathology↗

bioRxiv2020

Open Source ImmGen: network perspective on metabolic diversity among mononuclear phagocytes

We dissect metabolic variability of mononuclear phagocyte (MNP) subpopulations across different tissues through integrative analysis of three large scale datasets. Specifically, we introduce ImmGen MNP Open Source dataset that profiled 337 samples and extended previous ImmGen effort which included 202 samples of mononuclear phagocytes and their progenitors. Next, we analysed Tabula Muris Senis dataset to extract data for 51,364 myeloid cells from 18 tissues. Taken together, a compendium of data assembled in this work covers phagocytic populations found across 38 different tissues. To analyse common metabolic features, we developed novel network-based computational approach for unbiased identification of key metabolic subnetworks based on cellular transcriptional profiles in large-scale datasets. Using ImmGen MNP Open Source dataset as baseline, we define 9 metabolic subnetworks that encapsulate the metabolic differences within mononuclear phagocytes, and demonstrate that these features are robustly found across all three datasets, including lipid metabolism, cholesterol biosynthesis, glycolysis, and a set of fatty acid related metabolic pathways, as well as nucleotide and folate metabolism. We systematically define major features specific to macrophage and dendritic cell subpopulations. Among other things, we find that cholesterol synthesis appears particularly active within the migratory dendritic cells. We demonstrate that interference with this pathway through statins administration diminishes migratory capacity of the dendritic cells in vivo. This result demonstrates the power of our approach and highlights importance of metabolic diversity among mononuclear phagocytes.

immunology↗