Lack of Adipocytes Alters Hematopoiesis in Lipodystrophic Mice.
Fiche publication
Date publication
janvier 2018
Journal
Frontiers in immunology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr JOUZEAU Jean-Yves
Tous les auteurs :
Wilson A, Fu H, Schiffrin M, Winkler C, Koufany M, Jouzeau JY, Bonnet N, Gilardi F, Renevey F, Luther SA, Moulin D, Desvergne B
Lien Pubmed
Résumé
Adult hematopoiesis takes place in the perivascular zone of the bone cavity, where endothelial cells, mesenchymal stromal/stem cells and their derivatives such as osteoblasts are key components of bone marrow (BM) niches. Defining the contribution of BM adipocytes to the hematopoietic stem cell niche remains controversial. While an excess of medullar adiposity is generally considered deleterious for hematopoiesis, an active role for adipocytes in shaping the niche has also been proposed. We thus investigated the consequences of total adipocyte deletion, including in the BM niche, on adult hematopoiesis using mice carrying a constitutive deletion of the gene coding for the nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ). We show that lipodystrophic mice exhibit severe extramedullary hematopoiesis (EMH), which we found to be non-cell autonomous, as it is reproduced when wild-type donor BM cells are transferred into recipients. This phenotype is not due to a specific alteration linked to deletion, such as chronic inflammation, since it is also found in AZIP mice, another lipodystrophic mouse model with normal PPARγ expression, that display only very moderate levels of inflammation. In both models, the lack of adipocytes alters subpopulations of both myeloid and lymphoid cells. The CXCL12/CXCR4 axis in the BM is also dysregulated in an adipocyte deprived environment supporting the hypothesis that adipocytes are required for normal hematopoietic stem cell mobilization or retention. Altogether, these data suggest an important role for adipocytes, and possibly for the molecular interactions they provide within the BM, in maintaining the appropriate microenvironment for hematopoietic homeostasis.
Mots clés
AZIPtg/+ mice, PPARγ null mice, bone marrow adipocytes, extramedullary hematopoiesis, hematopoiesis, inflammation, lipodystrophy, non-cell autonomous alteration of hematopoiesis in PPARγ null mice
Référence
Front Immunol. 2018 ;9:2573