Fly research gives insight into human stem cell development and cancer

Public release date: 8-Mar-2012 [ | E-mail | Share ]

Contact: Phyllis Edelman pedelman@genetics-gsa.org 301-351-0896 Genetics Society of America

CHICAGO, IL March 8, 2012 Stem cells provide a recurring topic among the scientific presentations at the Genetics Society of America's 53rd Annual Drosophila Research Conference, March 7-11 at the Sheraton Chicago Hotel & Towers. Specifically, researchers are trying to determine how, within organs, cells specialize while stem cells maintain tissues and enable them to repair damage and respond to stress or aging. Four talks, one on Thursday morning and three on Sunday morning, present variations on this theme.

For a fertilized egg to give rise to an organism made up of billions or trillions of cells, a precise program of cell divisions must unfold. Some divisions are "asymmetric": one of the two daughter cells specializes, yet the other retains the ability to divide. Chris Q. Doe, Ph.D., professor of biology at the University of Oregon, compares this asymmetric cell division to splitting a sundae so that only one half gets the cherry. The "cherries" in cells are the proteins and RNA molecules that make the two cells that descend from one cell different from each other. This collecting of different molecules in different regions of the initial cell before it divides is termed "cell polarity."

Dr. Doe and his team are tracing the cell divisions that form a fly's nervous system. "Producing the right cells at the right time is essential for normal development, yet it's not well understood how an embryonic precursor cell or stem cell generates a characteristic sequence of different cell types," he says. Dr. Doe and his team traced the cell lineages of 30 neuroblasts (stem cell-like neural precursors), each cell division generating a daughter cell bound for specialization as well as a self-renewing neuroblast. The dance of development is a matter of balance. Self-renew too much, and a tumor results; not enough, and the brain shrinks.

Tracing a cell lineage is a little like sketching a family tree of cousins who share a great-grandparent except that the great-grandparent (the neuroblast) continually produces more cousins. "The offspring will change due to the different environments they are born into," says Dr. Doe.

Julie A. Brill, Ph.D., a principal investigator at The Hospital for Sick Children (SickKids) in Toronto, investigates cell polarity in sperm cells. These highly specialized elongated cells begin as more spherical precursor cells. Groups of developing sperm elongate, align, condense their DNA into tight packages, expose enzyme-containing bumps on their tips that will burrow through an egg's outer layers, form moving tails, then detach and swim away.

The Brill lab studies a membrane lipid called PIP2 (phosphatidylinositol 4,5-bisphosphate) that establishes polarity in developing male germ cells in Drosophila. "Reducing levels of PIP2 leads to defects in cell polarity and failure to form mature, motile sperm," Dr. Brill says. These experiments show that localization of the enzyme responsible for PIP2 production in the growing end of elongating sperm tails likely sets up cell polarity. Since loss of this polarity is implicated in the origin and spread of cancer, defects in the regulation of PIP2 distribution may contribute to human cancer progression, she adds.

Stephen DiNardo, Ph.D., professor of cell and developmental biology at the Institute for Regenerative Medicine at the University of Pennsylvania, is investigating how different varieties of stem cells in the developing fly testis give rise to germ cells and epithelial cells that ensheathe the germ cells, as well as being able to self-renew. For each of these roles, stem cells are guided by their environment, known as their "niche."

In the fly testis, we know not only the locations of the two types of stem cells whose actions maintain fertility, but of neighboring cells. "We study how these niche cells are first specified during development, how they assemble, and what signals they use. Elements of what we and others learn about this niche may well apply to more complex niches in our tissues," Dr. DiNardo explains.

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Fly research gives insight into human stem cell development and cancer