Amy Wagers
Department of Pathology
Room 620C
One Joslin Place
Boston, MA 02215
Tel: 617-309-3590
Fax: 617-309-2593
Bauer Center, Room 3-307
Harvard University
7 Divinity Ave.
Cambridge, MA 02138
Tel: 617-496-3046
Email: amy.wagers@joslin.harvard.edu
Email: amy.wagers@joslin.harvard.edu
Visit my lab page here.
The broad interest of our lab is to identify and characterize tissue-specific stem cell populations in adult animals. Current research focuses primarily on blood-forming (hematopoietic) and skeletal muscle stem cells in mice.
Biology and function of hematopoietic stem cells. Every year, thousands of patients undergo bone marrow or peripheral blood progenitor cell transplantation for the treatment of diverse diseases (including leukemia, lymphoma, immunodeficiency and others). The success of these transplants depends critically on the surprising ability of intravenously infused hematopoietic stem cells, which normally reside predominantly in the bone marrow, to accurately and efficiently migrate from the blood to the marrow of hematopoietically ablated transplant recipients and, once there, to expand and differentiate to repopulate the recipient’s pool of mature blood cells. While we previously demonstrated that the homing capacity of blood-forming stem cells likely makes use of pre-existing pathways that support the constitutive recirculation of these cells in normal animals, the mechanisms and regulators of these events remain largely unknown. We therefore are pursuing both genetic and cell biological approaches to defining genes and gene products that control the migration, expansion, differentiation and survival of blood-forming stem cells in normal animals and in transplant settings.
Adult skeletal muscle precursor cells. Currently, blood-forming stem cells are the only adult stem cell population that can be purified and used for the treatment of human disease. In order to develop equally robust cell therapies for the treatment of non-blood-cell-related disease, cells with equivalent regenerative function for non-blood tissues must be identified. Recent data from several investigators have suggested that blood-forming stem cells themselves may serve as such a source of regenerative cells for the repair of multiple organs; however, thus far, we have found no evidence to support a significant contribution from hematopoietic or bone marrow sources to the regeneration of non-blood tissues. Therefore, we have initiated studies to identify tissue-resident stem cell populations that function robustly to regenerate damaged adult tissues, and have recently succeeded in prospectively isolating a novel population of adult skeletal muscle precursor cells with robust myogenic activity. Future studies will be aimed at further defining cell lineage relationships in the differentiation of muscle stem and progenitor cells, as well as identifying signaling pathways and gene expression programs important for maintaining these muscle-resident cell populations. In addition, similar strategies will be applied to other adult tissues, including cardiac muscle and pancreas, to test the hypothesis that the adult tissues harbor as yet uncharacterized, isolatable stem cell populations that may support the repair of non-blood tissues.
References:
Eggan K, Jurga S, Gosden R, Min IM, Wagers AJ. Ovulated oocytes in adult mice derive from non-circulating germ cells. Nature 2006;441:1109-14.
Min IM, Pietramaggiori G, Kim FS, Passegue E, Stevenson KE, Wagers AJ. The transcription factor EGR1 controls both the proliferation and localization of hematopoietic stem cells. Cell Stem Cell 2008;2:380-391.
Cerletti M, Jurga S, Witczak CA, Hirshman MF, Shadrach JL, Goodyear LJ, Wagers AJ. Highly efficient, functional engraftment of skeletal muscle stem cells in dystrophic muscles. Cell 2008;134:37-47.
Young AP, Wagers AJ. Pax3 induces differentiation of juvenile skeletal muscle stem cells without transcriptional upregulation of canonical myogenic regulatory factors. J. Cell Sci. 2010;123:2632-9.