Stem Cell Differentiation Controlled by Two Related Proteins

Researchers have identified the mechanism that controls whether hematopoetic stem cells (HSC) remain undifferentiated or whether they transform into one of eight specialized types of blood cells.

Investigators at the University of Wisconsin (Madison, USA) studied the interaction of the GATA transcription factors, which are known to be important determinants of cell fate during hematopoiesis. They used chromatin immunoprecipitation analysis to show that the GATA-1 protein bound to a highly restricted upstream region of the 70-kb GATA-2 domain, despite the presence of more than 80 GATA sites throughout the domain. GATA-2 also bound to this region in the absence of GATA-1. Genetic complementation studies in GATA-1-null cells showed that GATA-1 rapidly displaced GATA-2, which was coupled to transcriptional repression. GATA-1 also displaced CREB-binding protein (CBP), despite the fact that GATA-1 bound CBP in other contexts. These findings were published July 11, 2003, in the online edition of the Proceedings of the National Academy of Sciences.

"Manipulations to expand stem cell numbers can cause the cells to lose their ability to remain stem cells,” explained senior author Dr. Emery Bresnick, professor of pharmacology at the University of Wisconsin. "Any mechanism that tells you how to maintain stem cell status and prevent differentiation is a good target for modulating and improving this whole process. We discovered a mechanism that is an excellent candidate for controlling the decision of whether the HSC should remain undifferentiated or form blood. It is a delicate balance between two highly related proteins, but if we can shift the balance by modulating this relationship, we can chose to increase the number of these limited HSC or stimulate hematopoiesis.”




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