Vascular Basement Membranes Establish a β2-Integrin-Dependent Macrophage-Preadipocyte Niche that Guides Adipose Tissue Fate

<title>Abstract</title> <p> Growing evidence suggests that tissue-resident immune cells actively shape tissue development, yet the underlying mechanisms remain unclear. We identify a vascular extracellular matrix (ECM) niche in white adipose tissue that directs progenitor fate through integrin-dependent immune-stromal interactions. Here, CD206 ^high Tim4 ⁺ macrophages reside along vascular basement membranes where they engage ICAM-1 ⁺ PDGFRα ⁺ committed preadipocytes via β2-integrin. Using mice lacking key vascular basement membrane components, together with single-cell RNA sequencing, high-resolution imaging, and organoid models, we show that endothelial basement membrane laminins control both the localization and non-inflammatory state of CD206 ^high Tim4 ⁺ macrophages, while also supporting preadipocyte positioning and persistence. These spatially confined macrophage-preadipocyte interactions are essential for terminal adipocyte differentiation and establish a microenvironment that maintains tissue structure and lipid balance. Our findings demonstrate that the vascular ECM establishes an immune-stromal niche that physically guides adipose tissue fate, offering a new framework for understanding how immune cells influence tissue development and metabolic homeostasis. </p>