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

Abstract

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.

The Role and Mechanism of the Vascular Endothelial Niche in Diseases: A Review

“…Colorectal cancer cells secreted exosome miR-25-3p, which targeted vascular endothelial growth factor (VEGF) receptor 2, zonula occludens 1, occludin, and claudin five on endothelial cells to induce vascular permeability and angiogenesis, forming a premetastatic niche for colorectal cancer metastasis ( Zeng et al, 2018a ). Additionally, in Lyl1 −/− mice, adipose stem cell vascular niche impairment led to decreased pericyte coverage with loss of vascular endothelial (VE)-cadherin and zonula occludens 1, resulting in premature adipose stem cell vascular niche depletion ( Hussain et al, 2021 ).…”