|Department:||Center for Reproductive Biology, Director & School of Molecular Biosciences|
|Credentials:||2004-Pd.D., Washington State University|
|Office:||Biotechnology/Life Sciences 302EA|
|Mailing Address:||Center for Reproductive Biology|
PO Box 647521
Pullman, WA 99164-7521
Male Germline Stem Cell Function
My laboratory studies the regulation of germline stem cell fate decisions in the mammalian testis. Spermatogenesis is a classic model of tissue-specific stem cell biology relying on the activity of spermatogonial stem cells and support from their cognate niche that is provided by contributions from testis somatic cell populations. Also, spermatogenesis is essential for the continuity of a species, contributes to genetic diversity, and determines sex ratios in most mammalian populations. Reduction in or loss of spermatogonial stem cell function disrupts spermatogenesis leading to reproductive failure in males. In addition, because spermatogonial stem cells are the only cells in the body that self-renew and contribute genes to the next generation, they provide an avenue to alter genes within a male’s germline. Aside from medical implications in humans, preservation of genetic lines of endangered species and expanded use of gametes from valuable food or companion animals represents a potential application of spermatogonial stem cell populations utilizing their capacity for regeneration of male germlines upon transplantation. Research in my laboratory involves deciphering; 1) molecular mechanisms within spermatogonial stem cells that control self-renewal and differentiation, 2) pathways controlling postnatal development of the spermatogonial stem cell pool to establish the adult stem cell population, and 3) determinants of the stem cell niche microenvironment within mammalian testes. The current focus is on investigating the role of basic helix-loop-helix (bHLH) proteins in controlling spermatogonial stem cell fate decisions, the influence of non-coding small RNAs on establishment of the spermatogonial stem cell pool, and identifying growth factors produced by testis somatic support cell populations that contribute to the niche microenvironment.
Helsel AR, Oatley MJ, Oatley JM. 2017. Glycolysis optimized conditions enhance maintenance of regenerative integrity in mouse spermatogonial stem cells during long-term culture. Stem Cell Reports. 2017 May 9;8(5):1430-1441. doi: 10.1016/j.stemcr.2017.03.004. Epub 2017 Apr 6.
Agrimson KS, Oatley MJ, Mitchell D, Oatley JM, Griswold MD, Hogarth CA. 2017. Retinoic acid deficiency leads to an increase in spermatogonial stem number in the neonatal mouse testis, but excess retinoic acid results in no change. Dev Biol. 2017 Dec 15;432(2):229-236. doi: 10.1016/j.ydbio.2017.10.002. Epub 2017 Oct 14.
Helsel AR, Yang QE, Oatley MJ, Lord T, Stablitzky F, Oatley JM. 2017. ID4 levels dictate the stem cell state in mouse spermatogonia. Development. Feb 15;144(4):624-634. doi: 10.1242/dev.146928. Epub 2017 Jan 13
Park K-E, Kaucher A, Sandmaier SES, Waqas MS, Powell A, Oatley MJ, Tibary A, Donovan DM, Blomberg LA, Lillico S, Whitelaw B, Mileham A, Telugu B, Oatley JM. 2017. Generation of germline ablated male pigs by CRISPR/Cas9 editing of the NANOS2 gene. Sci. Reports. 7: 40176.
Helsel AR, Oatley JM. 2017. Transplantation as a tool to study male germline stem cells. Methods Mol Biol. 1463: 155-172.
Mutoji K, Singh A, Nguyen T, Gildersleeve H, Kaucher A, Oatley M, Oatley JM, Velte E, Geyer C, Cheng K, McCarrey J, Hermann B. 2016. TSPAN8 expression distinguishes spermatogonial stem cells in the prepubertal testis. Biol. Reprod. 95: 117.
Teng Z, Oatley JM, Bradwell VJ, Zarkower D. 2016. DMRT1 is required for mouse spermatogonial stem cell maintenance and replenishment. PLoS Genetics. 12: e1006293.
Oatley MJ, Kaucher AV, Yang QE, Waqas MS, Oatley JM. 2016. Conditions for long-term culture of cattle undifferentiated spermatogonia. Biol. Reprod. 95: 14.
Hammoud SS, Low DHP, Yi C, Lee CL, Oatley JM, Payne CJ, Carrell DT, Guccione E, Cairns BR. 2015. Transcription and Imprinting Dynamics in Developing Postnatal Male Germline Stem Cells. Genes Dev. 29: 2312-24.
Geister KA, Brinkmeier ML, Cheung LY, Wendt J, Oatley MJ, Burgess DL, Seeley AH, Kozloff KM, Calvalcoli JD, Oatley JM, Camper SA. 2015. LINE-1 mediated insertion into poc1a (protein of centriole 1 a) causes growth insufficiency and male infertility in mice. PLoS Genetics. 11: e1005569.
Yang Q, Nagaoka S, Gwost I, Hunt PA, Oatley JM. 2015. Inactivation of retinoblastoma protein (Rb1) in the oocyte reveals a unifying mechanism of ovarian teratoma formation in mice. PLoS Genetics. 11: e1005355.
Hermann BP, Mutoji K, Velte EK, Ko D, Oatley JM, Geyer CB, McCarrey JR. 2015. Transcriptional and translational heterogeneity among neonatal mouse spermatogonia. Biol. Reprod. 92: 54.
Vrooman L, Oatley JM, Griswold JE, Hassold TJ, Hunt PA. 2015. Developmental estrogenic exposure alters the spermatogonial stem cell of the testis, permanently reducing meiotic recombination levels in the adult. PLoS Genetics. 11: e1004949.
Chan, F., et al. (2014). "Functional and molecular features of the Id4+ germline stem cell population in mouse testes." Genes Dev 28(12): 1351-1362.
Yang, Q. E. and J. M. Oatley (2014). "Spermatogonial stem cell functions in physiological and pathological conditions." Curr Top Dev Biol 107: 235-267.
Griswold, M. D. and J. M. Oatley (2013). "Concise review: Defining characteristics of mammalian spermatogenic stem cells." Stem Cells 31(1): 8-11.
Mistry, B. V., et al. (2013). "Differential expression of PRAMEL1, a cancer/testis antigen, during spermatogenesis in the mouse." PLoS One 8(4): e60611.
Yang, Q. E., et al. (2013). "Retinoblastoma protein (RB1) controls fate determination in stem cells and progenitors of the mouse male germline." Biol Reprod 89(5): 113.
Yang Q., Kaucher A.V., Kim D-W., Oatley M.J., Oatley J.M. 2013. CXCL12/CXCR4 signaling is required for maintenance of spermatogonial stem cells. J Cell Sci. Feb 15; 126(4): 1009–1020. PMCID: PMC4074255. PMID: 23239029, doi: 10.1242/jcs.119826
Yang Q., Racicot K.E., Kaucher A.V. Oatley M.J., Oatley J.M. 2013. MicroRNAs 221/222 regulate the undifferentiated state in mammalian male germ cells. Development. 140: 280-290.
Kaucher A.V., Oatley M.J., Oatley J.M. 2012. Neurog3 is a critical downstream effector of Stat3 regulated differentiation of mammalian stem and progenitor spermatogonia. Biol. Reprod. 86: 1-11.
Oatley MJ, Kaucher AV, Racicot KE, Oatley JM. 2011. Inhibitor of DNA binding 4 is expressed selectively by single spermatogonia in the male germline and regulates the self-renewal of spermatogonial stem cells in mice. Biol. Reprod. 85: 347-356.
Oatley MJ, Racicot KE, Oatley JM. 2011. Sertoli cells dictate spermatogonial stem cell niches in the mouse testis. Biol. Reprod. 84: 639-645.
Oatley JM, Kaucher AV, Avarbock MR, Brinster RL. 2010. Regulation of spermatogonial stem cell differentiation by STAT3 signaling. Biol. Reprod. 83: 427-433.
Wu X, Oatley JM, Oatley MJ, Kaucher AV, Avarbock MR, Brinster RL. 2010. The POU domain transcription factor POU3F1 is an important regulator of GDNF induced survival and self-renewal of mouse spermatogonial stem cells. Biol. Reprod. 82: 1103-1111.
Oatley JM, Oatley MJ, Avarbock MR, Tobias JW, Brinster RL. 2009. Colony stimulating factor 1 is an extrinsic regulator of mouse spermatogonial stem cell self-renewal. Development 136: 1191-1199.
Schmidt JA, Oatley JM, Brinster RL. 2009. Female mice delay reproductive aging in males. Biol. Reprod.; 80: 1009-1014.
Oatley JM, Brinster RL. 2008. Regulation of spermatogonial stem cell self-renewal in mammals. Ann. Rev. Cell Dev. Biol.; 24: 263-286.
Oatley JM, Avarbock MR, Brinster RL. Glial cell line-derived neurotrophic factor regulation of genes essential for mouse spermatogonial stem cell self-renewal is dependent on Src family kinase signaling. J. Biol. Chem., 2007; 282: 25842-25851.
Oatley, J.M., Avarbock, M.R., Telaranta, A.I., Fearon, D.T., Brinster, R.L. 2006. Identifying genes important for spermatogonial stem cell self-renewal and survival. Proc. Natl. Acad. Sci. USA 103:9524-9529.