Participation in Weekly Discussions

Students will be expected to read each assigned paper thoroughly. To aid in this, students will be asked to email the instructor with 2-3 questions or comments about the papers before each session (due at least 1 hour before the session begins). Students will also be expected to attend all of the sessions and be prepared to discuss any figure from the papers each week.

Written Paper (Due in Ses #10)

Students will write a 2-3 page proposal (double-spaced) report of an experiment to extend upon or clarify one of the papers discussed in class. This proposal should include a summary of the main results of the original paper, the design and methods of the proposed experiment (including controls), and the meaning of the possible results of this experiment. Be sure to include references relevant to the experimental design.

Oral Presentation (Ses #14)

For the final assignment, students will select a paper from list below and give a 15-minute presentation of the work on the last day of class (Ses #14). This presentation should consist of an introduction explaining how this paper is relevant to one of the topics covered in the course, an explanation of the design and methods of the experiments in each figure of the paper, the authors' conclusions, and the significance of the work.

List of Papers for Oral Presentation

Hanna, J., et al. "Treatment of Sickle Cell Anemia Mouse Model with iPS Cells Generated from Autologous Skin." Science 318 (2007): 1920-1923. This is a "proof of principle" study of the use of patient-derived induced pluripotent stem (iPS) cells. These authors derive iPS cells from the skin of a mouse model of sickle cell anemia, then use gene targeting to correct the sickle cell defect within these cells and differentiate the cells in culture to become hematopoietic stem cells, then transplant them back into the donor in order to correct the sickle cell defect within the animal.
Molina, M. D., E. Salo, and F. Cebria. "The BMP Pathway is Essential for Re-specification and Maintenance of the Dorsoventral Axis in Regenerating and Intact Planarians." Dev Biol 311 (2007): 79-94. These authors find that the Bone Morphogenic Protein (BMP) signaling pathway is required for specification of the dorso-ventral axis during planarian regeneration and homeostasis. Both the secreted protein BMP and the transcriptional effector of the pathway Smad1 are shown to be required for lateral regeneration but not for transverse regeneration. In addition, the dorsal side of these knockdown animals becomes ventralized.
Conboy, I. M., M. J. Conboy, A. J. Wagers, E. R. Girma, I. L. Weissman, and T. A. Rando. "Rejuvenation of Aged Progenitor Cells by Exposure to a Young Systemic Environment." Nature 433 (2005): 760-4. Aging is known to cause a decreased renewal potential of skeletal muscle tissue by satellite cells and decreased proliferation of hepatocytes in the liver. These authors find that exposure of these organs to blood serum from younger animals via parabiotic fusion results in an increased ability to maintain skeletal muscle and liver tissue.
Hammarlund, M., E. M. Jorgensen, and M. J. Bastiani. "Axons Break in Animals Lacking ß-Spectrin." J Cell Biol 176 (2007): 268-75. The axons of neurons in many different animals are known to regenerate. These authors find that axons regenerate in the nematode C. elegans. In a mutant deficient for beta-spectrin function, axons within these animals spontaneously break, and then regenerate. In this mutant, axon fragility is seen to be dependent upon the activity of animal movement. This could become a genetically tractable system for investigation of the molecular and cellular basis for axon regeneration.
Ohori, Y., S. Yamamoto, M. Nagao, M. Sugimori, N. Yamamoto, K. Nakamura, and M. Nakafuku. "Growth Factor Treatment and Genetic Manipulation Stimulate Neurogenesis and Oligodendrogenesis by Endogenous Neural Progenitors in the Injured Adult Spinal Cord." J Neurosci 46 (2006): 11948-60. These induce endogenous neuronal stem cells within an injured spinal cord to differentiate into neurons by adding exogenous growth factors and also by expressing transgenes from retroviruses.
Nir, T., D. A. Melton, and Y. Dor. "Recovery from Diabetes in Mice by ß Cell Regeneration." J Clin Invest 117 (2007): 2553-61. These authors employ a transgenic strategy to deplete pancreatic beta cells from an adult animal, inducibly, and find that surviving beta-cells can repopulate the pancreas. Significantly, the authors show that immunosuppressants normally used for kidney transplantation also inhibit beta cell regeneration.
Bender Kim, C. F., E. L. Jackson, A. E. Woolfenden, S. Lawrence, I. Babar, S. Vogel, D. Crowley, R. T. Bronson, and T. Jacks. "Identification of Bronchioalveolar Stem Cells in Normal Lung and Lung Cancer." Cell 121 (2005): 823-35. These authors identify epithelial stem cells of the lung (branchioalveolar stem cells, BASCs) and show that these cells proliferate in vivo, and can self-renew and differentiate into lung cell types in vitro. In a lung cancer model driven by inducible expression of oncogenic k-ras, these BASCs become more highly proliferative, suggesting that mutations in BASCs may create a cancer stem cell which maintains tumors in patients with lung cancer.
Brack, A. S., M. J. Conboy, S. Roy, M. Lee, C. J. Kuo, C. Keller, and T. A. Rando. "Increased Wnt Signaling During Aging Alters Muscle Stem Cell Fate and Increases Fibrosis." Science 317 (2007): 807-810. As aging proceeds, skeletal tissue replacement is impaired and instead becomes increasingly populated with non-muscle connective tissue, a process generally termed "fibrosis." In this follow-up paper to "Rejuvenation of aged progenitor cells by exposure to a young systemic environment," the same laboratory finds that satellite cells from older individuals have a decreased ability to differentiate into skeletal muscle and an increased tendency to form connective tissue. Furthermore, they show that increased Wnt signaling during aging is responsible for this lineage switch.
Malanchi, I., et al. "Cutaneous Cancer Stem Cell Maintenance is Dependent on ß-Catenin Signaling." Nature 452 (2008): 650-4. Are tumors maintained by a pool of cancer stem cells? These authors show that in a mouse model in which cutaneous (skin) tumors are generated by chemical carcinogenesis, tumors display an increase in the number of cells similar in expression patterns to normal skin stem cells (i.e., CD34-positive) residing in the bulge of hair follicles. These stem cell-like tumor cells are shown to be capable of forming similar tumors when transplanted into normal individuals and therefore may have the capability of self-renewal. The authors find that cutaneous cancer stem cells have elevated levels of canonical Wnt signaling through beta-catenin, and they find that beta-catenin is required for maintenance of the cutaneous tumors likely because it is also found to be required to maintain the CD34-positive cancer stem cells.