| First Author | Garbuzov A | Year | 2018 |
| Journal | Stem Cell Reports | Volume | 10 |
| Issue | 2 | Pages | 553-567 |
| PubMed ID | 29337115 | Mgi Jnum | J:333239 |
| Mgi Id | MGI:6759238 | Doi | 10.1016/j.stemcr.2017.12.009 |
| Citation | Garbuzov A, et al. (2018) Purification of GFRalpha1+ and GFRalpha1- Spermatogonial Stem Cells Reveals a Niche-Dependent Mechanism for Fate Determination. Stem Cell Reports 10(2):553-567 |
| abstractText | Undifferentiated spermatogonia comprise a pool of stem cells and progenitor cells that show heterogeneous expression of markers, including the cell surface receptor GFRalpha1. Technical challenges in isolation of GFRalpha1+ versus GFRalpha1- undifferentiated spermatogonia have precluded the comparative molecular characterization of these subpopulations and their functional evaluation as stem cells. Here, we develop a method to purify these subpopulations by fluorescence-activated cell sorting and show that GFRalpha1+ and GFRalpha1- undifferentiated spermatogonia both demonstrate elevated transplantation activity, while differing principally in receptor tyrosine kinase signaling and cell cycle. We identify the cell surface molecule melanocyte cell adhesion molecule (MCAM) as differentially expressed in these populations and show that antibodies to MCAM allow isolation of highly enriched populations of GFRalpha1+ and GFRalpha1- spermatogonia from adult, wild-type mice. In germ cell culture, GFRalpha1- cells upregulate MCAM expression in response to glial cell line-derived neurotrophic factor (GDNF)/fibroblast growth factor (FGF) stimulation. In transplanted hosts, GFRalpha1- spermatogonia yield GFRalpha1+ spermatogonia and restore spermatogenesis, albeit at lower rates than their GFRalpha1+ counterparts. Together, these data provide support for a model of a stem cell pool in which the GFRalpha1+ and GFRalpha1- cells are closely related but show key cell-intrinsic differences and can interconvert between the two states based, in part, on access to niche factors. |
