The Faculty in Reproductive Biology at Illinois

  Marie-Claude Hofmann

   Associate Professor
   Institute for Genomic Biology and Department of Veterinary Biosciences

   To e-mail Dr. Hofmann use: mhofmann@uiuc.edu

Regulation of spermatogonial stem cells
Many questions about the biology of stem cells remain unanswered. Some of these are: what defines a stem cell, or “stemness”, what is the influence of the stem cell “niche” in regulating stem cell self-renewal and differentiation, and what are the intracellular signaling pathways underlying stem cell behavior. Answering these questions will bring us closer to effectively engineer stem cells and tissues for regenerative therapy, and provide new insights into the etiology of certain cancers.

My research program uses spermatogonial stem cells as a model to answer these questions. These stem cells are pluripotent, giving rise to daughter cells that belong to the three embryonic germ layers.

I. Signaling in spermatogonial stem cell development:
Spermatogonial stem cells and their progeny are contained in the germinal epithelium of the seminiferous tubules, in close association with the nursing Sertoli cells. Regulatory mechanisms, mediated by growth factors produced by Sertoli cells, induce or inhibit the proliferation, differentiation and further development of the germ cells. We are interested in understanding the molecular mechanisms that control spermatogonial cell fate decision by the growth factor glial cell line-derived neurotrophic factor (GDNF). We recently demonstrated that at least one pathway triggered by GDNF involves the activation of Src family kinases and the up-regulation of N-Myc. We are further elucidating signaling networks that converge onto N-Myc and probing its role for self-renewal/differentiation.

2. Cytotoxicity of nanoparticles in the germ line:
Gametogenesis is a complex biological process that is particularly sensitive to environmental insults such as chemicals. Many chemicals have a negative impact on the germ line, either by directly affecting the germ cells, or indirectly through their action on the somatic nursing cells. Ultimately, these effects can inhibit fertility, and may have negative consequences on the development of the offspring. It has been recently shown that nanoparticles can cross the blood-brain and blood-testis barriers. However, despite the wide application of nanomaterials, there is a serious lack of information concerning their impact on human health. The purpose of our studies is to assess the toxicity of specific nanoparticles in the germ line.

3. Development of nanoparticles for the modulation and real time visualization of signaling pathways:
While certain nanoparticles can be toxic, others can be functionalized and used to probing signaling pathways in real time in vivo. Due to the small size of a stem cell population, the amount of protein that we can isolate from those cells limits our studies of signaling pathways. We are thus devising, in collaboration with the University of Dayton Research Institute, biocompatible nanoparticles that will enable us to visualize and modulate signaling pathways in living cells.

Selected Publications

Braydich-Stolle, L., Kostereva, N.V., Dym, M, and Hofmann, M.C. 2007. Role of Src kinases and N-Myc in spermatogonial stem cell proliferation. Dev Biol., In press. Online December 12, 2006.

Cooke, P.S., Hess, R.A., Simon, L., Schlesser, H.N., Carnes, K., Tyagi, G., Hofmann, M.C., and Murphy, K.M. 2006. The transcription factor Ets-Related Molecule (ERM) is essential for spermatogonial stem cell maintenance and self-renewal. Animal Reproduction, 3:98–107.

Hess, R.A., Cooke, P.S., Hofmann, M.C., and Murphy, K.M. 2006. Mechanistic insights into the regulation of the spermatogonial stem cell niche. Cell Cycle, 5(11):1164–70. [Abstract]

Braydich-Stolle, L., Dym, M., and Hofmann, M.C. 2005. Role of glial cell line-derived neurotrophic factor (GDNF) in germ-line stem cell fate. Ann. NY Acad. Sciences, 1061:94–9

Braydich-Stolle, L., Hussain, S., Schlager, J., and Hofmann, M.C. 2005. In vitro cytotoxicity of nanoparticles in mammalian germ-line stem cells. Toxicol. Sci., 88(2):412–19. [Abstract]

Chen, C., Ouyang, W., Grigura, V., Zhou, Q., Carnes, K., Lim, H., Zhao, G.Q., Arber, S., Kurpios, N., Murphy, T.L., Cheng, A.M., Hassell, J.A., Chandrashekar, V., Hofmann, M.C., Hess, R.A., and Murphy, K.M. 2005. ERM is required for the transcriptional control of the spermatogonial stem cell niche. Nature, 436(7053):1030–4. [Abstract]

Hofmann, M.C., Braydich-Stolle, L., and Dym, M. 2005. Isolation of male germ line stem cells; influence of GDNF. Dev Biol., 279(1):114–24. [Abstract]

Hofmann, M.C., Braydich-Stolle, L., Dettin, L., Johnson, E., and Dym, M. 2005. Immortalization of mouse germ-line stem cells. Stem Cells, 23(2):200–210. [Abstract]

View Marie-Claude Hofmann's Publications at the National Library of Medicine (PubMed)

Last updated January 20, 2007

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