TSPAN8 Expression Distinguishes Spermatogonial Stem Cells in the Prepubertal Mouse Testis

Overview

Journal Biol Reprod

Publisher Oxford University Press

Specialty Reproductive Medicine

Date 2016 Oct 14

PMID 27733379

Citations 29

Authors

Kazadi Mutoji

Anukriti Singh

Thu Nguyen

Heidi Gildersleeve

Amy V Kaucher

Melissa J Oatley

Jon M Oatley

Ellen K Velte

Christopher B Geyer

Keren Cheng

John R McCarrey

Brian P Hermann

Affiliations

Soon will be listed here.

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.

Citing Articles

Characterisation and hierarchy of the spermatogonial stem cell compartment in human spermatogenesis by spectral cytometry using a 16-colors panel.

Lapoujade C, Blanco M, Givelet M, Gille A, Allemand I, Lenez L Cell Mol Life Sci. 2024; 82(1):15.

PMID: 39725808 PMC: 11671462. DOI: 10.1007/s00018-024-05496-6.

Role of Dual Specificity Phosphatase 1 (DUSP1) in influencing inflammatory pathways in macrophages modulated by lipoproteins.

Kumaresan V, Hung C, Hermann B, Seshu J bioRxiv. 2024; .

PMID: 39605372 PMC: 11601599. DOI: 10.1101/2024.11.20.624562.

Differential protein repertoires related to sperm function identified in extracellular vesicles (EVs) in seminal plasma of distinct fertility buffalo () bulls.

Badrhan S, Karanwal S, Pal A, Chera J, Chauhan V, Patel A Front Cell Dev Biol. 2024; 12:1400323.

PMID: 39135778 PMC: 11318068. DOI: 10.3389/fcell.2024.1400323.

Spermatogonial stem cell technologies: applications from human medicine to wildlife conservation†.

Damyanova K, Nixon B, Johnston S, Gambini A, Benitez P, Lord T Biol Reprod. 2024; 111(4):757-779.

PMID: 38993049 PMC: 11473898. DOI: 10.1093/biolre/ioae109.

Postnatal development of mouse spermatogonial stem cells as determined by immunophenotype, regenerative capacity, and long-term culture-initiating ability: a model for practical applications.

Song Y, Zhang X, Desmarais J, Nagano M Sci Rep. 2024; 14(1):2299.

PMID: 38280889 PMC: 10821885. DOI: 10.1038/s41598-024-52824-8.

References

Brinster R, Zimmermann J . Spermatogenesis following male germ-cell transplantation. Proc Natl Acad Sci U S A. 1994; 91(24):11298-302. PMC: 45218. DOI: 10.1073/pnas.91.24.11298. View

Kubota H, Avarbock M, Brinster R . Spermatogonial stem cells share some, but not all, phenotypic and functional characteristics with other stem cells. Proc Natl Acad Sci U S A. 2003; 100(11):6487-92. PMC: 164473. DOI: 10.1073/pnas.0631767100. View

Song H, Bettegowda A, Lake B, Zhao A, Skarbrevik D, Babajanian E . The Homeobox Transcription Factor RHOX10 Drives Mouse Spermatogonial Stem Cell Establishment. Cell Rep. 2016; 17(1):149-164. PMC: 5063083. DOI: 10.1016/j.celrep.2016.08.090. View

Ebata K, Zhang X, Nagano M . Expression patterns of cell-surface molecules on male germ line stem cells during postnatal mouse development. Mol Reprod Dev. 2005; 72(2):171-81. DOI: 10.1002/mrd.20324. View

Kluin P, de Rooij D . A comparison between the morphology and cell kinetics of gonocytes and adult type undifferentiated spermatogonia in the mouse. Int J Androl. 1981; 4(4):475-93. DOI: 10.1111/j.1365-2605.1981.tb00732.x. View

Suzuki H, Sada A, Yoshida S, Saga Y . The heterogeneity of spermatogonia is revealed by their topology and expression of marker proteins including the germ cell-specific proteins Nanos2 and Nanos3. Dev Biol. 2009; 336(2):222-31. DOI: 10.1016/j.ydbio.2009.10.002. View

Ballow D, Meistrich M, Matzuk M, Rajkovic A . Sohlh1 is essential for spermatogonial differentiation. Dev Biol. 2006; 294(1):161-7. DOI: 10.1016/j.ydbio.2006.02.027. View

Yoshinaga K, Ogawa M, Hayashi S, Kunisada T, Fujimoto T, Nishikawa S . Role of c-kit in mouse spermatogenesis: identification of spermatogonia as a specific site of c-kit expression and function. Development. 1991; 113(2):689-99. DOI: 10.1242/dev.113.2.689. View

Jaenisch R, Young R . Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell. 2008; 132(4):567-82. PMC: 4142810. DOI: 10.1016/j.cell.2008.01.015. View

10.

Hermann B, Sukhwani M, Winkler F, Pascarella J, Peters K, Sheng Y . Spermatogonial stem cell transplantation into rhesus testes regenerates spermatogenesis producing functional sperm. Cell Stem Cell. 2012; 11(5):715-26. PMC: 3580057. DOI: 10.1016/j.stem.2012.07.017. View

11.

Zhou Z, Shirakawa T, Ohbo K, Sada A, Wu Q, Hasegawa K . RNA Binding Protein Nanos2 Organizes Post-transcriptional Buffering System to Retain Primitive State of Mouse Spermatogonial Stem Cells. Dev Cell. 2015; 34(1):96-107. DOI: 10.1016/j.devcel.2015.05.014. View

12.

Herlevsen M, Schmidt D, Miyazaki K, Zoller M . The association of the tetraspanin D6.1A with the alpha6beta4 integrin supports cell motility and liver metastasis formation. J Cell Sci. 2003; 116(Pt 21):4373-90. DOI: 10.1242/jcs.00760. View

13.

Lavoie J, Creskey M, Muradia G, Bell G, Sherman S, Gao J . Brief Report: Elastin Microfibril Interface 1 and Integrin-Linked Protein Kinase Are Novel Markers of Islet Regenerative Function in Human Multipotent Mesenchymal Stromal Cells. Stem Cells. 2016; 34(8):2249-55. DOI: 10.1002/stem.2385. View

14.

Pan L, North H, Sahni V, Jeong S, McGuire T, Berns E . β1-Integrin and integrin linked kinase regulate astrocytic differentiation of neural stem cells. PLoS One. 2014; 9(8):e104335. PMC: 4123915. DOI: 10.1371/journal.pone.0104335. View

15.

Busada J, Chappell V, Niedenberger B, Kaye E, Keiper B, Hogarth C . Retinoic acid regulates Kit translation during spermatogonial differentiation in the mouse. Dev Biol. 2014; 397(1):140-9. PMC: 4268412. DOI: 10.1016/j.ydbio.2014.10.020. View

16.

Busada J, Geyer C . The Role of Retinoic Acid (RA) in Spermatogonial Differentiation. Biol Reprod. 2015; 94(1):10. PMC: 4809555. DOI: 10.1095/biolreprod.115.135145. View

17.

Trapnell C, Roberts A, Goff L, Pertea G, Kim D, Kelley D . Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat Protoc. 2012; 7(3):562-78. PMC: 3334321. DOI: 10.1038/nprot.2012.016. View

18.

Hermann B, Hornbaker K, Maran R, Heckert L . Distal regulatory elements are required for Fshr expression, in vivo. Mol Cell Endocrinol. 2006; 260-262:49-58. PMC: 1764205. DOI: 10.1016/j.mce.2006.01.017. View

19.

Endo T, Romer K, Anderson E, Baltus A, de Rooij D, Page D . Periodic retinoic acid-STRA8 signaling intersects with periodic germ-cell competencies to regulate spermatogenesis. Proc Natl Acad Sci U S A. 2015; 112(18):E2347-56. PMC: 4426408. DOI: 10.1073/pnas.1505683112. View

20.

Sada A, Hasegawa K, Pin P, Saga Y . NANOS2 acts downstream of glial cell line-derived neurotrophic factor signaling to suppress differentiation of spermatogonial stem cells. Stem Cells. 2011; 30(2):280-91. DOI: 10.1002/stem.790. View