β-catenin-mediated Wnt signaling may contribute to the self-renewal of hematopoietic stem cells and proliferation in some malignancies. We now show that expression of constitutively active β-catenin in normal lymphoid or myeloid progenitors generated uncommitted cells with multilineage differentiation potential. Inappropriate gene expression occurred in cells destined to produce either cell type and caused corresponding changes in their characteristics. For example, forced activation of β-catenin quickly increased C/EBPα while reducing EBF and Pax-5 in lymphoid progenitors that then generated myeloid cells. Inversely, EBF dramatically increased in transduced myeloid progenitors and lymphocytes were produced. The results indicate that ectopic activation of β-catenin destabilizes lineage fate decisions and confers some, but not all, stem cell properties on committed progenitors.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Infectious Diseases