Identification of EOMES-expressing spermatogonial stem cells and their regulation by PLZF.
Manju SharmaAnuj SrivastavaHeather E FairfieldDavid BergstromWilliam F FlynnRobert E BraunPublished in: eLife (2019)
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 Plzf +/+ and Plzf lu/lu 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 Plzf lu/lu mice, suggesting that PLZF regulates their proliferative activity and that EOMES+ SSCs are lost through proliferative exhaustion in Plzf lu/lu mice. Single cell RNA sequencing of EOMES+ cells from Plzf +/+ and Plzf lu/lu mice support the conclusion that SSCs are hierarchical yet heterogeneous.
Keyphrases
- stem cells
- wild type
- single cell
- transcription factor
- growth factor
- high fat diet induced
- rna seq
- cell proliferation
- induced apoptosis
- signaling pathway
- metabolic syndrome
- type diabetes
- mesenchymal stem cells
- oxidative stress
- insulin resistance
- binding protein
- acute lymphoblastic leukemia
- endoplasmic reticulum stress
- acute myeloid leukemia