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A Harvard Medical School Affiliate
Welcome to the Joslin Research Website
Joslin Investigator:
Amy Wagers, PhD
Investigator Specifics:
Professional Details:
Publications
CV not available
Member of Section:
Developmental & Stem Cell Biology
Core Director:
Flow Cytometry Core
Current Fellows, Students, or Lab Members:
Massimiliano Cerletti
Shane Mayack
Irene Min
Arthur Young
Past Fellows, etc.:
Kedar Gumaste
Sara Jurga
Torey Mack
Jessica Price
Tony Yang
Investigators
Adjunct Investigators
Fellows & Team Members
DERC Cores
Research Sections
Joslin Resources
Amy Wagers, Ph.D.
Investigator
Joslin Diabetes Center
Assistant Professor of Pathology
Harvard Medical School
Core Co-Director: Flow Cytometry
5/1/2004 -
Stem Cells in Adult Tissues
The broad interest of the WAGERS LAB is to identify and characterize tissue-specific stem cell populations in adult animals. This work focuses on understanding the factors controlling the migration and expansion of bone marrow-derived and blood-forming (hematopoietic) stem cells in mice, as well as developing methods for the isolation and manipulation of distinct stem and progenitor cell populations from adult mouse skeletal muscle.
Biology and function of hematopoietic stem cells.
Every year, more than 45,000 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.
Reconstitution of the blood system by a single hematopoietic stem cell (HSC)
. Hematopoietic colonies in the bone marrow of a mouse transplanted with a single GFP-marked HSC. GFP fluorescence is shown in green and nuclear staining with Hoechst 33342 is shown in blue.
Myogenic colony formed by clonally isolated adult skeletal muscle progenitor cells.
GFP-labeled (green) single-sorted precursor cells generate progeny cells expressing the differentiated myocyte marker myosin heavy chain (red). Nuclear staining with Hoechst 33342 is shown in blue.
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 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 the future, 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.
Recent publications:
1. Wright DE, Wagers AJ, Gulati AP, Johnson FL, Weissman IL. Physiological migration of hematopoietic stem and progenitor cells. Science 294: 1933, 2001.
2. Wagers AJ, Sherwood RI, Christensen JC, and Weissman, IL. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science 297:2256, 2002.
3. Wagers AJ and Weissman IL. Plasticity of adult stem cells. Cell, 116:639, 2004.
4. Conboy IM, Conboy MJ, Wagers AJ, Girma ER, Weissman IL, Rando TA. Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature, 433:760, 2005.
5. Passegue E, Wagers AJ, Giuriato S, Anderson WC, Weissman IL. Global analysis of proliferation and cell cycle gene expression in the regulation of hematopoietic stem and progenitor cell fates. J. Exp. Med., 202:1599, 2005.
6. Eggan K, Jurga S, Gosden R, Min IM, and Wagers AJ. Ovulated oocytes in adult mice derive from non-circulating germ cells. Nature, 441:1109, 2006.
Biographical Sketch
Dr. Wagers is a Principal Investigator in the Section on Developmental and Stem Cell Biology as well as an Assistant Professor of Pathology at Harvard Medical School. She received her doctoral degree in Immunology and Microbial Pathogenesis from Northwestern University, and completed postdoctoral fellowship training in the laboratory of Irving Weissman, M.D., at Stanford University School of Medicine. She is a recipient of the Burroughs Wellcome Fund Career Award in Biomedical Sciences and Smith Family New Investigator Award.
