"Understanding the genetic circuitry that orchestrates development of each specialized cell type," Singh added, "should enable us to manipulate it for our own purposes."
The researchers focused on how hematopoietic stem cells developed into one of two types of white blood cells: macrophages or neutrophils. Macrophages are the long-lived garbage disposals of the immune system, indiscriminately engulfing and digesting cellular debris and pathogens. The shorter-lived neutrophils are the immune system's vultures, flocking to the site of an infection to target and ingest invading organisms.
Although both cell types come from cells known as myeloid progenitors, each type relies on its own set of functionally active genes to carry out its particular role in fighting infection. A major scientific puzzle has been how and why immature hematopoietic stem cells initially express genes that are characteristic of both cell lineages.
Until recently, however, there was no experimental system that researchers could manipulate to solve this puzzle. A few years ago, Singh and colleagues identified a transcription factor called PU.1 that acts as the primary signal, a central genetic switch to initiate development of myeloid progenitor cells. Other researchers identified a rival transcription factor, C/EBP.
Cells from mice bred in Singhs lab to lack PU.1 allowed the researchers to manipulate the cells' decision-making machinery by introducing different amounts of PU.1. When the researchers int
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Contact: John Easton
john.easton@uchospitals.edu
773-702-6241
University of Chicago Medical Center
30-Aug-2006