Functional Complementation Between Beta-Catenin And Hoxa9 Sustains Hsc Self-Renewal In A Prmt1-Dependent Manner

Self-renewal is a fundamental property essential for both normal and malignant hematopoietic stem cells (HSCs). While we and others have previously shown that activation of Hoxa9 or β-catenin enhances HSC self-renewal, its inactivation has modest impacts on adult HSCs and their malignant counterparts (Cobas et al., 2004; Lawrence et al., 2005; Siriboonpiputtana et al., 2017; Smith et al., 2011; So et al., 2004; Zhao et al., 2007), suggesting the presence of complementary pathways capable of mediating self-renewal in the absence of either protein. However, simultaneous inactivation of other key Hox genes involved in hematopoietic self-renewal including Hoxb3/b4 did not yield additional hematopoietic phenotypes in the Hoxa9 knockout (KO) background (Magnusson et al., 2007). Similarly, suppression of γ-catenin in β-catenin KO mice did not result in additional hematopoietic defects, and exhibited largely normal hematopoietic functions (Koch et al., 2008). Therefore, the alternative pathways that support hematopoietic self-renewal upon inactivation of Hoxa9 or β-catenin remain largely unknown.