The Molecular Basis of B-cell Lineage Commitment
This extract was created in the absence of an abstract.
Excerpt
All cell types of the blood are generated from a pluripotent hematopoietic stem cell through developmentally restricted progenitors that undergo lineage commitmentand subsequent differentiation along a single pathway.Despite extensive analyses of hematopoietic cytokinesand transcription factors, little is known about the molecular mechanisms underlying lineage commitment. Thisprocess is thought to irreversibly restrict the developmental fate of a progenitor cell to a single lineage by establishing a unique gene expression program (Fig. 1). Expression analyses at the single-cell level have recentlydemonstrated that multipotent progenitor cells promiscuously activate genes from different lineage-affiliated programs, although often at a low level (Hu et al. 1997). Thismultilineage priming of gene transcription is also evidentat the chromatin level, where selective enhancer regionsof lineage-specific genes are made accessible inhematopoietic progenitors (Cross and Enver 1997). It istherefore thought that transcription factors involved inlineage commitment must fulfill a dual role. They shouldrepress the transcription of lineage-inappropriate genesand, at the same time, activate the expression of furtherlineage-specific genes (Fig. 1). As a consequence, thegene expression program of a single lineage is stabilized,and alternative lineage fates of the progenitor cell are suppressed at lineage commitment (for review, see Enverand Greaves 1998; Rothenberg 1998)...
