TSPAN8 Expression Distinguishes Spermatogonial Stem Cells in the Prepubertal Mouse Testis. Issue 6 (1st December 2016)

• Record Type: Journal Article
• Authors: Mutoji, Kazadi; Singh, Anukriti; Nguyen, Thu; Gildersleeve, Heidi; Kaucher, Amy V.; Oatley, Melissa J.; Oatley, Jon M.; Velte, Ellen K.; Geyer, Christopher B.; Cheng, Keren; McCarrey, John R.; Hermann, Brian P.
• Is Part Of: Biology of reproduction. Volume 95:Issue 6(2016)
• Publication Date: 2016-12-01
• Subjects: epigenetics -- single-cell -- spermatogonial stem cells -- surface marker -- transcriptome -- transplantation; Reproduction -- Periodicals; Biology; Reproduction; Reproduction; Electronic journals; Periodicals; Periodicals; 571.805
• DOI: 10.1095/biolreprod.116.144220
• Languages: English
• ISSNs: 0006-3363

Abstract

Abstract: Precise separation of spermatogonial stem cells (SSCs) from progenitor spermatogonia that lack stem cell activity and are committed to differentiation remains a challenge. To distinguish between these spermatogonial subtypes, we identified genes that exhibited bimodal mRNA levels at the single-cell level among undifferentiated spermatogonia from Postnatal Day 6 mouse testes, including Tspan8, Epha2, and Pvr, each of which encode cell surface proteins useful for cell selection. Transplantation studies provided definitive evidence that a TSPAN8-high subpopulation is enriched for SSCs. RNA-seq analyses identified genes differentially expressed between TSPAN8-high and -low subpopulations that clustered into multiple biological pathways potentially involved in SSC renewal or differentiation, respectively. Methyl-seq analysis identified hypomethylated domains in the promoters of these genes in both subpopulations that colocalized with peaks of histone modifications defined by ChIP-seq analysis. Taken together, these results demonstrate functional heterogeneity among mouse undifferentiated spermatogonia and point to key biological characteristics that distinguish SSCs from progenitor spermatogonia.