Quiescence is a common character of many stem cells. Low metabolic activity in these cells may function to minimize the potential damaging effects of stress, minimize the number of cells needed for replenishment, and may occupy unique niches. These cells are found in many adult human tissues, even in the tissues of the central nervous system. These naturally occurring stem cells however, are rare and difficult to isolate so a mechanistic understanding of their integrated cellular activities is largely unknown. We recently learned that the primordial germ cells (PGC) of the sea urchin are quiescent. From a highly active early embryonic cell, they rapidly and dramatically change their metabolic pathways, decrease their protein synthesis, have low mRNA turnover and diminished transcription, and reduced mitochondrial activity. These cells are quiescent at a time when the remainder of the embryo multiplies to thousands of cells with many unique gene and protein expression patterns. Following the quiescent period, the PGCs rapidly return to normal cellular activity. Thus, the phenotype is prolonged, inclusive, highly penetrant, and transient. Resolution of the phenotype will require large numbers of naturally occurring, isolated PGCs, high throughput molecular manipulations, quantitative biochemical approaches, and excellent clarity for in vivo optics ? features ideally suited for sea urchin embryos. This application will interrogate the molecular mechanism of this transient quiescence and the dramatic phenotypic changes in the stem cells of the germ line. Stem cell quiescence is shared by many stem cell types, in and out of the germ line, but sparingly few models are present to explore such mechanisms in abundance, in naturally occurring cells, and in vivo. Overall the novelty and impact of this work includes: 1) germline stem cells using oxidative glycolysis but without proliferation ? distinct from the Warburg effect; 2) broad, quantitative quiescence characters; 3) integration of metabolism with molecular mechanisms for quiescence; 4) analysis of quiescence on developmental potential of the stem cell, and 5) the cells studied are primordial germ cells, a cell type found in all sexually reproducing animals. Coupled with a tractable model system for study, this proposal provides outstanding potential to add to an exciting field of both basic and clinical interest for generation of sperm and eggs in the adult.

Public Health Relevance

Quiescent stem cells are present throughout the human body, including the central nervous system, with the potential to replace adult tissues. Quiescent stem cells are even present in cancers, and by virtue of their quiescence can escape chemotherapy. Unfortunately, quiescent stem cells are generally quite rare and difficult to study. However, we recently discovered quiescent stem cells of the germ cell lineage in a sea urchin that provides an excellent model for understanding entry and departure from stem cell quiescence. We can isolate, manipulate, and interrogate large numbers of these cells within the intact embryo, or in culture conditions, to discover the molecular mechanism of this prevalent, but understudied, stem cell character.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Cellular, Molecular and Integrative Reproduction Study Section (CMIR)
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Salazar, Desiree Lynn
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Brown University
Schools of Medicine
United States
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Tilahun, Belay; Tesfaye, Anteneh; Muleta, Diriba et al. (2018) Isolation and Molecular Identification of Lactic Acid Bacteria Using 16s rRNA Genes from Fermented Teff (Eragrostis tef (Zucc.)) Dough. Int J Food Sci 2018:8510620
Fresques, Tara M; Wessel, Gary M (2018) Nodal induces sequential restriction of germ cell factors during primordial germ cell specification. Development 145:
Brayboy, Lynae M; Knapik, Laura O; Long, Sokunvichet et al. (2018) Ovarian hormones modulate multidrug resistance transporters in the ovary. Contracept Reprod Med 3:26
Oulhen, Nathalie; Wessel, Gary (2017) A quiet space during rush hour: Quiescence in primordial germ cells. Stem Cell Res 25:296-299