A New Genetic Tool for Lineage Tracing of Mitotic Cells in Mice Abstract Mitosis represents one of the most important signatures of somatic stem cells and progenitor cells. The proliferative activity of these cells is essential for supporting tissue functions, replacing damaged or aged tissues, and maintaining tissue homeostasis. Due to the limitations of lineage tracing tools, we still know little about how and to what extent somatic stem or progenitor cells contribute to the function and homeostasis of somatic tissues. The adaptive immune system provides one of the best examples to study the dynamic relationship between the proliferative burst of progenitors and tissue homeostasis. During an immune response to pathogens antigen-specific lymphocytes undergo vigorous clonal expansion. These newly generated effector cells are quickly removed through apoptosis following pathogen clearance. A small fraction of antigen-experienced cells develops into memory cells, which are long lived and are capable of further expansion during subsequent exposure to the same antigen. The generation and homeostatic maintenance of memory lymphocytes are critical for long lasting immunity. Thus far, the origin and fate of memory lymphocytes are still not completely understood. We are developing a unique Cre/lox mediated mitotic recombination system in mice. Using this reporter system, any proliferating cells in adult mice may be pulse labeled with a visible marker for long term tracing of these cells and their descendants. We plan to use this genetic marking system to label and trace memory T cells derived from an immune response to pathogens. We will examine the development, location, and maintenance of memory T cells after primary and secondary pathogen exposure. Because the experimental system is designed to mark the descendants of any dividing cells, the system should also be useful for tracing and analyzing clonal behavior of progenitors or stem cells in tissue types beyond the lymphoid system. We anticipate a broad application of this marking system in the fields such as tissue regeneration, aging, and immunological memory.

Public Health Relevance

The proposed research will provide a new research tool for experimental analysis of immune cells and stem cells in animal models. The outcome will impact our understanding of immune memory and stem cell behaviors.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Exploratory/Developmental Grants (R21)
Project #
8R21OD011200-02
Application #
8334077
Study Section
Cellular and Molecular Immunology - A Study Section (CMIA)
Program Officer
Mirochnitchenko, Oleg
Project Start
2011-09-16
Project End
2014-01-31
Budget Start
2012-08-01
Budget End
2014-01-31
Support Year
2
Fiscal Year
2012
Total Cost
$196,250
Indirect Cost
$71,250
Name
Duke University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705