A two-step process appears to regulate cell fate decisions for many types of developing cells, according to researchers from the University of Chicago.
This finding sheds light on a puzzling behavior. For some differentiating stem cells, the first step leads not to a final decision but to a new choice. In response to the initial chemical signal, these cells take on the genetic signatures of two different cell types. It often requires a second signal for them to commit to a single cellular identity.
In the Aug. 25 2006 issue of Cell, the researchers, working with hematopoietic stem cells, which give rise to the many types of blood cells, show how "pioneer transcription factors" trigger the first step, pushing these stem cells towards this mixed lineage, midway between two related cell types -- in this case between a macrophage and a neutrophil.
Then one of two rival "secondary factors" activates the genes that lead to one cell type and shuts down the genes that lead to the alternative.
Understanding the circuitry that controls these decisions is central to learning how different kinds of stem cells develop. It provides insights into how to transform stem cells into therapeutically useful cells and suggests possible new treatments for leukemias, in which a persistent mixed lineage seems to drive cancerous proliferation.
Although the researchers worked only with blood-forming stem cells, they suspect that the same basic regulatory principles govern cell type determination in other tissues such as skin, brain and intestine.
"We see elements of this framework of primary and secondary cell-fate determinants throughout the hematopoietic system," said study author Harinder Singh, the Louis Block Professor of Molecular Genetics & Cell Biology and a Howard Hughes Medical Institute Investigator at the University of Chicago, "and we suspect such networks also regulate cell fate in other systems."
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Contact: John Easton
john.easton@uchospitals.edu
773-702-6241
University of Chicago Medical Center
30-Aug-2006