Dr. Jon Oatley
Research & Interests
In mammals, homeostasis relies on stem cells replenishing tissue lineages with differentiating cells that are continually lost due to cytotoxic injury and terminal differentiation. In embryonic and neonatal development these stem cells are also tasked with establishing tissue lineages while setting aside a self-renewing population that will remain undifferentiated and be sustained throughout life. To carry out their functions, stem cells possess the capacity for both self-renewal to maintain a pool of stem cells and generation of progenitor cells that are set on a pathway of differentiation. These fate decisions are tightly regulated by influences from microenvironments referred to as ‘niches’. In general, stem cell niches are themselves tissue-specific being composed of a growth factor milieu and architectural support that are dictated by resident support cells. The possible immortal nature of stem cells provides a potential avenue for regenerative medicine to treat a variety of degenerative diseases caused by loss of tissue homeostasis. Achieving this goal relies on the deciphering of molecular mechanisms within stem cells that control fate decisions and defining the components that constitute niche microenvironments.
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 sub-fertility or infertility 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. Furthermore, information gained from studying spermatogonial stem cells may be applicable to other tissue-specific stem cell populations.
Research 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.
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. Epub Ahead of Print.
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 JM, Avarbock MR, Telaranta AI, Fearon DT, Brinster RL. 2006. Identifying genes important for spermatogonial stem cell self-renewal and survival. Proc. Natl. Acad. Sci. USA 103: 9524-9529.
Ryu B-Y, Orwig KE, Oatley JM, Avarbock MR, Brinster RL. 2006. Effects of aging and niche microenvironment on spermatogonial stem cell self-renewal. Stem Cells 24: 1505-1511.
Oatley, JM, Brinster RL. Spermatogonial Stem Cells. Methods Enzymol., 2006; 419:259-282.