HOXB4-mediated Enhanced Self-renewal of Committed Hematopoietic Progenitors

Stemness is the capacity of cells to 1) differentiate into distinct cell types and 2) self-renew. Self-renewal is the ability of a cell to produce identical daughter cells upon division and resist differentiation. Both hematopoietic and leukemic stem cells follow a hierarchy defined by varying capacities for self-renewal. Therefore, understanding the control of self-renewal is of vital importance. The Homeobox family of transcription factors, including HOXB4, plays an important role in the regulation of self-renewal. However, the specific stages in differentiation at which HOXB4 maintains self-renewal remain unknown. I identified two phenotypes of hematopoietic progenitors that sustain self-renewal in a subset of hematopoietic lineages given exogenous HOXB4. These findings provide new support to the idea that the cell sustaining self-renewal given exogenous HOXB4 is not multipotent, and contribute new specificity by finding that susceptibility to immortalization by exogenous HOXB4 is confined to specific early stages in hematopoiesis.M.Sc