In most mammalian tissues, homeostasis is maintained by tissue stem cells that function through continued self-renewal and differentiation. Despite the importance of this cell fate decision to tissue homeostasis, the general rules by which stem cell progeny commit to the paths of self- renewal or differentiation are largely unknown. Most current paradigms presume that environmental cues determine the fate of individual stem cell progeny. Unexpectedly, our preliminary data and published studies show that rodent spermatogonial stem cell (SSC) progeny autonomously elicit self-renewal and differentiation in a stochastic manner with constant probability, and that this balance may be regulated by extrinsic cues. These findings point to new mechanisms guiding mammalian SSC self-renewal and differentiation, which will likely prove relevant to other stem cell types. Here w propose to investigate the physiological regulation and the molecular components governing mouse SSC stochastic fate choice. Specifically, we will examine the role of specific internal and external factors that can influence fate choice of SSC progeny and identify novel SSC intrinsic factors that promote self-renewal through a genetic screen. Insights from this study may provide the basis for new therapeutic interventions that restore fertility and optimize birth control.

Public Health Relevance

In adult tissues, the principal means for replacing cells lost during normal organ function or disease depends on a rare population of cells known as tissue stem cells. These cells possess unique abilities to not only replace other cells but also renew themselves. Our proposed studies of the decision-making mechanisms of adult tissue stem cells will lead to new insights into aging and many common disease conditions including infertility and cancer.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21HD067666-01A1
Application #
8512509
Study Section
Development - 1 Study Section (DEV1)
Program Officer
Moss, Stuart B
Project Start
2013-09-17
Project End
2015-08-31
Budget Start
2013-09-17
Budget End
2014-08-31
Support Year
1
Fiscal Year
2013
Total Cost
$188,125
Indirect Cost
$63,125
Name
Tulane University
Department
Anatomy/Cell Biology
Type
Schools of Arts and Sciences
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118