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Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):4949-53. Epub 2005 Mar 23.

Contingent gene regulatory networks and B cell fate specification.

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  • 1Howard Hughes Medical Institute and Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA. hsingh@midway.uchicago.edu

Abstract

The B cell developmental pathway represents a leading system for the analysis of regulatory circuits that orchestrate cell fate specification and commitment. Considerable progress has been achieved within the past decade in the identification and genetic analysis of various regulatory components. These components include the transcription factors PU.1, Ikaros, Bcl11a, E2A, EBF, and Pax-5, as well as the cytokine receptors Flk2 and IL-7R. Experimental evidence of connectivity among the regulatory components is used to assemble sequentially acting and contingent gene regulatory networks. Transient signaling inputs, self-sustaining positive feedback loops, and cross-antagonism among alternate cell fate determinants are key features of the proposed networks that instruct the development of B lymphocyte precursors from hematopoietic stem cells.

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