Stem Cells

Stem cells hold the key to the continual renewal of many tissues in our bodies. In addition, the in vitro manipulation of stem cells holds much promise in regenerative medicine. Unfortunately, there are severe limitations in our knowledge of the regulation of stem cells. These limitations compromise both our understanding of normal tissue renewal, as well as the facility with which stem cell populations can be grown and manipulated in vitro. We are trying to remove such limitations by studying stem cells within their natural environment, the niche by using Drosophila spermatogenesis as a model stem cell system. This allows us to bring to bear modern approaches to uncover new regulatory factors that govern stem cell behavior.

Through genomic-scale analyses, we have identified several genes whose expression is enriched in stem cells or their niche cells, and are studying their function. These include a transcriptional repressor, zfh1, that we find maintains somatic stem cell fate, a pioneer protein, lines, that we find keeps stem cells from differentiating into niche cells, and a novel secreted factor necessary for continued survival of germline stem cells. But our contributions extend beyond the simple identification of new regulator factors. They have also revealed conceptually new facets of control over stem cell lineages. For example, we know now that two different types of stem cells communicate in a common niche; we know that as a stem cell pool is initially established in a tissue, a regulatory pathway parses some cells as stem cells and others as niche cells. In these, and similar other examples, we can now attack how these conceptually interesting facets of stem cell biology are controlled.

Given the deep conservation of developmental mechanisms across species, we are confidant that concepts revealed by our studies in the fruitfly will apply to some mammalian stem cell lineages.

Representative Publications on Stem Cell Function

Leatherman, J.L. and DiNardo, S.(2008) “zfh-1 controls somatic stem cell self-renewal in the drosophila testis and nonautonomously influences germline stem cell self-renewal.” Cell Stem Cell 3, 44-54.

Franklin-Dumont, T. M., Chatterjee, C., Wasserman, S. A. and DiNardo, S. (2007) “A novel EIF4G homolog, Off-schedule, couples translational control to meiosis and differentiation in Drosophila spermatocytes”. Development 134, 2851 - 61

N. Terry, N. Tulina, E. Matunis and DiNardo, s. (2006) "Novel intrinsic and extrinsic regulators revealed by profiling Drosophila testis stem cells within their niche". Developmental Biology 294, 246 – 257.

Wallenfang, M., Nayak, R. and DiNardo, S. (2006) “Dynamics of the male germline stem cell population during aging of Drosophila melanogaster”.Aging Cell 5, 297-304 (with cover).