In Lyl1−/− mice, adipose stem cell vascular niche impairment leads to premature development of fat tissues

Lyl1 encodes a hematopoietic‐ and endothelial‐specific bHLH transcription factor. Lyl1‐deficient mice are viable, but they display mild hematopoietic and vascular defects. Specifically, LYL1 is required for the maturation and stabilization of blood vessel endothelial adherens junctions. Here, we report that young adult Lyl1−/− mice exhibit transient overweight associated with general expansion of adipose tissue, without signs of metabolic disorder and unrelated to food intake. The increased fat tissue development in Lyl1−/− mice resulted from earlier differentiation of adipose stem cells (ASCs) into adipocytes through noncell autonomous mechanisms. Specifically, we found that in Lyl1−/− mice, the adipose tissue vascular structures are immature, as indicated by their high permeability, reduced coverage by pericytes, lower recruitment of VE‐cadherin and ZO1 at cell junctions, and more prone to angiogenesis. Together, our data show that in Lyl1−/− mice, the impaired vascular compartment of the adipose niche promotes ASC differentiation, leading to early adipocyte expansion and premature ASC depletion. Our study highlights the major structural role of the adipose tissue vascular niche in coordinating stem cell self‐renewal and differentiation into adipocytes. In Lyl1‐deficient mice, the impaired vascular compartment of the adipose niche promotes triggering of adipose stem cell (ASC) differentiation, leading to premature ASC depletion, early adipocyte expansion, and overweight. In Lyl1‐deficient mice, the vascular structures of adipose tissues are immature, prone to angiogenesis and consequently, lead to progenitor exhaustion in the adipose tissue vascular niche. BAT, brown adipose tissue; EC, endothelial cells; WAT, white adipose tissue.