Identification of EOMES-expressing spermatogonial stem cells and their regulation by PLZF

Long-term maintenance of spermatogenesis in mammals is supported by GDNF, an essential growth factor required for spermatogonial stem cell (SSC) self-renewal. Exploiting a transgenic GDNF overexpression model, which expands and normalizes the pool of undifferentiated spermatogonia between and mice,...

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Bibliographic Details
Published in:eLife 2019-05, Vol.8
Main Authors: Sharma, Manju, Srivastava, Anuj, Fairfield, Heather E, Bergstrom, David, Flynn, William F, Braun, Robert E
Format: Article
Language:English
Subjects:
Age
Animals
Busulfan
Cell Differentiation - genetics
Cell Proliferation - genetics
Cell Self Renewal - genetics
Cell self-renewal
Developmental Biology
EOMES
Gene expression
Gene Expression Regulation, Developmental - genetics
Genetic aspects
Genetic engineering
Glial cell line-derived neurotrophic factor
Male
Mice
Observations
PLZF
Population
Promyelocytic Leukemia Zinc Finger Protein - genetics
Ribonucleic acid
RNA
RNA sequencing
RNA-Seq
Spermatogenesis
Spermatogenesis - genetics
Spermatogonia
Spermatogonia - cytology
Spermatogonia - metabolism
spermatogonial stem cells
Stem cell transplantation
Stem cells
Stem Cells - cytology
Stem Cells - metabolism
T-Box Domain Proteins - genetics
Testis - growth & development
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Summary:Long-term maintenance of spermatogenesis in mammals is supported by GDNF, an essential growth factor required for spermatogonial stem cell (SSC) self-renewal. Exploiting a transgenic GDNF overexpression model, which expands and normalizes the pool of undifferentiated spermatogonia between and mice, we used RNAseq to identify a rare subpopulation of cells that express EOMES, a T-box transcription factor. Lineage tracing and busulfan challenge show that these are SSCs that contribute to steady state spermatogenesis as well as regeneration following chemical injury. EOMES+ SSCs have a lower proliferation index in wild-type than in mice, suggesting that PLZF regulates their proliferative activity and that EOMES+ SSCs are lost through proliferative exhaustion in mice. Single cell RNA sequencing of EOMES+ cells from and mice support the conclusion that SSCs are hierarchical yet heterogeneous.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.43352