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 non-cell 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. © AlphaMed Press 2020 SIGNIFICANCE STATEMENT: The transcription factor lymphoblastic leukemia-derived sequence 1 (LYL1) is required for the maturation and stabilization of blood vessels. Depending on their permeability properties, blood vessels can support either stem cell quiescence or activation. This study showed that in Lyl1-deficient mice, the vascular structures of adipose tissues are permeable, poorly covered by pericytes and pro-angiogenic, thus promoting adipose stem cell differentiation. This study highlights for the first time LYL1 role in the vascular niche maintenance in adipose tissue.
© 2020 AlphaMed Press.

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