Among the hottest topics in current research are the potential uses for stem cells. Stem cell research has captured public attention as a possible way to facilitate new treatments, and perhaps cures, for a wide variety of afflictions. However, scientists are still learning how to coax pluripotent stem cells to differentiate into specialized cell types, a first step in what may eventually revolutionize the field of medicine.

Multiple types of stem cells are being used in current stem cell research, including embryonic stem cells, embryonic germ cells, and adult stem cells. Sources of adult stem cells include bone marrow, blood, skeletal muscle, the brain, dental pulp, and the liver, among others. Harinder Singh, Ph.D., Louis Block Professor of Molecular Genetics and Cell Biology and Investigator in the Howard Hughes Medical Institute, and his team have focused their work on hematopoietic stem cells (HSCs), the most studied of adult stem cells. Their findings, published in the 12 October 2004 issue of Developmental Cell, suggest that the transformation of a stem cell does not happen by altering a single gene; rather it results from a hierarchical regulatory network of transcription factors.

Unlike embryonic stem cells, HSCs have already started down the path to becoming a specialized cell - in this case, a blood cell. Five key transcription factors are involved in the creation of B cells: PU.1, Ikaros, E2A, EBF, and PAX5. However, the specific sequence of events and interactions among these molecules are poorly defined. Singh and his team have begun to order these transcription factors into a hierarchical regulatory network that stimulates HSCs to become committed B cells.

"There's a back and forth between the regulators that are controlling the genes and signaling molecules," says Singh. "In the hierarchical scheme, there are early acting regulators (PU.1 and Ikaros) that induce the signaling systems, signals through those systems then induce a secondary set of regulatory molecules, specifically E2A, EBF and PAX5.

The secondary regulators may re-inforce the expression of the signaling systems that induced them, thereby generating a positive feedback loop. We're tracing the molecular circuitry for a single developmental sequence, specifically, the path from hematopoietic stem cellto antibody-producing B cell. But there are actually at least ten different paths of this sort, each of them culminating in the generation of a distinct cell type of the immune or blood system," says Singh.

Singh sees great value in this discovery and its potential to impact the field of medicine. He describes the value as being two-fold.
"One is that by manipulating these networks you could more efficiently generate particular cells for therapeutic purposes," says Singh. "The other idea, which is somewhat more speculative, is that we could generate new types of cells altogether, ones that are hybrids of cells already existing in the human body. In both cases, based on our research, molecular biologists are going to have to shift from focusing on the manipulation of single genes to regulating a series of genetic components to move the field forward."

FOREFRONT
The Division of the Biological Sciences is proud to announce the appointment of two new Professors and Chairmen for the Departments of Psychiatry and Medicine...

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DISCOVERIES
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DEVELOPMENT
Development is on pace to meet a goal of $65 million in FY2005. Midway through the fiscal year, approximately $30 million has been contributed, and the Spark Discovery campaign has raised more than $420 million...

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Started in 2004, Achieving Breakthroughs is a major UCH initiative with significant BSD participation and support. BSD faculty can learn more about the initiative in upcoming faculty meetings in early 2005...

Dollars and Sense
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ACADEMIC AFFAIRS
Recent Recruitemnts and Appointments of Biological Sciences Division Faculty

ACCOLADES
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