Steve DiNardo

Professor of Cell and Developmental Biology

• Functional Identification of the Actual and Potential Stem Cell Compartments in Mouse Spermatogenesis (PDF, 1.41mb)
• A Vasculature-Associated Niche for Undifferentiated Spermatogonia in the Mouse Testis (PDF, 799mb)
• Presentation (PPT, 29.3mb)

Selected References

• That there are HSCs
  • Till, E. and E. A. McCulloch (1961). "A direct measurement of radiation sensitivity of normal mouse bone marrow cells." Mutation Research 14: 213-222.
  • Siminovitch, L., E. A. McCulloch and J. E. Till (1963). "The Distribution of Colony-Forming Cells among Spleen Colonies." J Cell Physiol 62: 327-36.
  • Spangrude, G. J., S. Heimfeld and I. L. Weissman (1988). "Purification and characterization of mouse hematopoietic stem cells." Science 241(4861): 58-62.
• There must be an HSC niche
  •    Schofield, R. (1978). "The relationship between the spleen colony-forming cell and the haemopoietic stem cell." Blood Cells 4(1-2): 7-25.
• Identifying an HSC niche
  • Taichman, R. S. and S. G. Emerson (1998). "The role of osteoblasts in the hematopoietic microenvironment." Stem Cells 16(1): 7-15.
  • Calvi, L. M., G. B. Adams, K. W. Weibrecht, J. M. Weber, D. P. Olson, M. C. Knight, R. P. Martin, E. Schipani, P. Divieti, F. R. Bringhurst, L. A. Milner, H. M. Kronenberg and D. T. Scadden (2003). "Osteoblastic cells regulate the haematopoietic stem cell niche." Nature 425(6960): 841-6.
  • Zhang, J., C. Niu, L. Ye, H. Huang, X. He, W. G. Tong, J. Ross, J. Haug, T. Johnson, J. Q. Feng, S. Harris, L. M. Wiedemann, Y. Mishina and L. Li (2003). "Identification of the haematopoietic stem cell niche and control of the niche size." Nature 425(6960): 836-41.
  • Kiel, M. J., O. H. Yilmaz, T. Iwashita, C. Terhorst and S. J. Morrison (2005). "SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells." Cell 121(7): 1109-21.
• Neural Stem Cells
  • Johe, K. K., T. G. Hazel, T. Muller, M. M. Dugich-Djordjevic and R. D. McKay (1996). "Single factors direct the differentiation of stem cells from the fetal and adult central nervous system." Genes Dev 10(24): 3129-40.
  • Capela, A. and S. Temple (2002). "LeX/ssea-1 is expressed by adult mouse CNS stem cells, identifying them as nonependymal." Neuron 35(5): 865-75.
• A neural Niche (it’s a vascular niche)
  • Palmer, T. D., A. R. Willhoite and F. H. Gage (2000). "Vascular niche for adult hippocampal neurogenesis." J Comp Neurol 425(4): 479-94.
  • Shen, Q., S. K. Goderie, L. Jin, N. Karanth, Y. Sun, N. Abramova, P. Vincent, K. Pumiglia and S. Temple (2004). "Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells." Science 304(5675): 1338-40.
• (An oddity – NSCs can differentiate endothelial cells = cells of their putative niche....):
  • Wurmser, A. E., K. Nakashima, R. G. Summers, N. Toni, K. A. D'Amour, D. C. Lie and F. H. Gage (2004). "Cell fusion-independent differentiation of neural stem cells to the endothelial lineage." Nature 430(6997): 350-6.
• NSC fates are “derived” by in vitro cultivation
  • Gabay, L., S. Lowell, L. L. Rubin and D. J. Anderson (2003). "Deregulation of dorsoventral patterning by FGF confers trilineage differentiation capacity on CNS stem cells in vitro." Neuron 40(3): 485-99.
  • Mukouyama, Y. S., B. Deneen, A. Lukaszewicz, B. G. Novitch, H. Wichterle, T. M. Jessell and D. J. Anderson (2006). "Olig2+ neuroepithelial motoneuron progenitors are not multipotent stem cells in vivo." Proc Natl Acad Sci U S A 103(5): 1551-6.
• Asymmetric division of fruitfly neuroblast cells
  • Yu, F., C. T. Kuo and Y. N. Jan (2006). "Drosophila neuroblast asymmetric cell division: recent advances and implications for stem cell biology." Neuron 51(1): 13-20.
• Spermatogonial Stem Cells: Transplantation / Repopulation
  • Brinster, R. L. and J. W. Zimmermann (1994). "Spermatogenesis following male germ-cell transplantation [see comments]." Proceedings of the National Academy of Sciences of the United States of America 91(24): 11298-302.
  • Nagano, M., M. R. Avarbock and R. L. Brinster (1999). "Pattern and kinetics of mouse donor spermatogonial stem cell colonization in recipient testes." Biol Reprod 60(6): 1429-36.
  • Shinohara, T., K. E. Orwig, M. R. Avarbock and R. L. Brinster (2000). "Spermatogonial stem cell enrichment by multiparameter selection of mouse testis cells." Proc Natl Acad Sci U S A 97(15): 8346-51.
  • Kubota, H., M. R. Avarbock and R. L. Brinster (2003). "Spermatogonial stem cells share some, but not all, phenotypic and functional characteristics with other stem cells." Proc Natl Acad Sci U S A 100(11): 6487-92.
• Spermatogonial Stem Cells: The Fruit Fly
  • Lineage tracing –
    • Gönczy, P. and S. DiNardo (1996). "The germ line regulates somatic cyst cell proliferation and fate during Drosophila spermatogenesis." Development 122(8): 2437-2447.
    • Margolis, J. and A. Spradling (1995). "Identification and behavior of epithelial stem cells in the Drosophila ovary." Development 121: 3797 - 3807.
• Self-renewal signaling through Jak / STAT
  • Kiger, A. A., D. L. Jones, C. Schulz, M. B. Rogers and M. T. Fuller (2001). "Stem cell self-renewal specified by JAK-STAT activation in response to a support cell cue." Science 294(5551): 2542-5.
  • Tulina, N. and E. Matunis (2001). "Control of stem cell self-renewal in Drosophila spermatogenesis by JAK-STAT signaling." Science 294(5551): 2546-9.
• Oriented divisions of the GSC
  • Yamashita, Y. M., D. L. Jones and M. T. Fuller (2003). "Orientation of asymmetric stem cell division by the APC tumor suppressor and centrosome." Science 301(5639): 1547-50.
• Dedifferentiation to regenerate stem cells
  • Brawley, C. and E. Matunis (2004). "Regeneration of male germline stem cells by spermatogonial dedifferentiation in vivo." Science 304(5675): 1331-4.
  • Kai, T. and A. Spradling (2004). "Differentiating germ cells can revert into functional stem cells in Drosophila melanogaster ovaries." Nature 428(6982): 564-9.
• Stem cell aging
  • Wallenfang, M. R., R. Nayak and S. DiNardo (2006). "Dynamics of the male germline stem cell population during aging of Drosophila melanogaster." Aging Cell 5(4): 297-304.
  • Boyle, M., C. Wong, M., Rocha, C., and D. Jones (2007) Decline in Self-Renewal Factors Contributes to Aging of the Stem Cell Niche in the Drosophila Testis. Cell Stem Cell 1, 470–478
• Hematopoietic stem cell aging
  • Chambers, S. M., C. A. Shaw, C. Gatza, C. J. Fisk, L. A. Donehower and M. A. Goodell (2007). "Aging hematopoietic stem cells decline in function and exhibit epigenetic dysregulation." PLoS Biol 5(8): e201.
• Spermatogonial Stem Cells: Genetic control in mammals
  • Meng, X., M. Lindahl, M. E. Hyvonen, M. Parvinen, D. G. de Rooij, M. W. Hess, A. Raatikainen-Ahokas, K. Sainio, H. Rauvala, M. Lakso, J. G. Pichel, H. Westphal, M. Saarma and H. Sariola (2000). "Regulation of cell fate decision of undifferentiated spermatogonia by GDNF." Science 287(5457): 1489-93.
  • Yomogida, K., Y. Yagura, Y. Tadokoro and Y. Nishimune (2003). "Dramatic expansion of germinal stem cells by ectopically expressed human glial cell line-derived neurotrophic factor in mouse Sertoli cells." Biol Reprod 69(4): 1303-7.
  • Buaas, F. W., A. L. Kirsh, M. Sharma, D. J. McLean, J. L. Morris, M. D. Griswold, D. G. de Rooij and R. E. Braun (2004). "Plzf is required in adult male germ cells for stem cell self-renewal." Nat Genet 36(6): 647-52.
  • Costoya, J. A., R. M. Hobbs, M. Barna, G. Cattoretti, K. Manova, M. Sukhwani, K. E. Orwig, D. J. Wolgemuth and P. P. Pandolfi (2004). "Essential role of Plzf in maintenance of spermatogonial stem cells." Nat Genet 36(6): 653-9.
• Ngn3 lineage marking
  • Yoshida, S., A. Takakura, K. Ohbo, K. Abe, J. Wakabayashi, M. Yamamoto, T. Suda and Y. Nabeshima (2004). "Neurogenin3 delineates the earliest stages of spermatogenesis in the mouse testis." Dev Biol 269(2): 447-58.

Course Schedule