Genetic networks that regulate B lymphopoiesis.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Medina
Kay L
KL
Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, Chicago, Illinois 60367, USA.
Singh
Harinder
H
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D038041:Lymphopoiesis / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D051941:fms-Like Tyrosine Kinase 3
D011518:Proto-Oncogene Proteins; D020395:Receptors, Interleukin-7; D014157:Transcription Factors; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3