Genetic networks that regulate B lymphopoiesis

Abstract

Purpose of review: The B cell developmental pathway represents a leading model within the hematopoietic system for the analysis of genetic networks, which orchestrate cell fate specification and commitment. Considerable progress is being achieved in the characterization of regulatory components that comprise such networks and examining their connectivity. These components include the cytokine receptors Flk2 and IL-7R as well as the transcription factors PU.1, Ikaros, Bcl11a, E2A, EBF, and Pax-5. Based on new experimental evidence, a comprehensive model is proposed that invokes sequentially acting and inter-dependent regulatory modules that instruct the generation of B cell precursors from multipotential hematopoietic progenitors.

Recent findings: The transcription factor PU.1 regulates the generation of lymphoid progenitors that express Flk2 and IL-7R. IL-7R receptor signaling appears to function in specification of the B cell fate. The transcription factor EBF can bypass the requirement for PU.1 and E2A in early B cell development. Pax-5 expression and function are contingent on EBF.

Summary: Assembly of gene regulatory networks involved in cell fate specification may facilitate the efficient and directed generation of lineage-specific hematopoietic progenitors from embryonic stem cells for therapeutic purposes.