LRP5 and LRP6 are required for maintaining self-renewal and differentiation of hematopoietic stem cells

The canonical Wnt signaling pathway has been demonstrated as a critical role in the self-renewal, proliferation and differentiation of Hematopoietic Stem Cells (HSCs), but the functions are indeterminacy in adult HSCs since the different experimental systems using gain- or loss- functions mice models. Low-density lipoprotein receptor-related proteins 5 and 6 (LRP5 and LRP6) are important co-receptors in the canonical Wnt/β-catenin pathway. In this study, the knockout mice models were established for adult HSC investagation via conditional ablation of LRP5 and LRP6 in adult hematopoiesis by Vav-Cre Loxp system. We found the HSC numbers were diminished due to the decreased proliferation and cell cycle. To investigate the molecular mechanisms, RNA-seq was performed using HSC cells isolated from WT and dKO mice. HSC (CD34-Flt3- Lin-ScaI+C-Kithigh cells) purified by FACS sorting