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Monash researchers seek to reveal potential of testicular stem cells

25 June 2014
Robin Hobbs and Juho-Antti Mäkelä

Within the mammalian testis reside stem cells that are essential for sperm production and maintaining male fertility throughout life. A team of researchers based at Monash’s Australian Regenerative Medicine Institute (ARMI) and the Department of Anatomy and Developmental Biology are seeking to better understand how the function of these stem cells is regulated and the potential for these cells to be a new form of pluripotent stem cells.

Leading the ARMI research team is Dr Robin Hobbs who has recently joined the Stem Cells Australia consortium as a Chief Investigator. Robin has long been interested in the unique stem cells of the mammalian testis – referred to as spermatogonial stem cells or SSCs. While these stem cells have been observed to spontaneously convert to pluripotent embryonic-like stem cells upon culture in the laboratory, the process that regulates this ‘reprogramming’ remains poorly understood. Robin, together with post-doctoral research fellow Juho-Antti Mäkelä, are working to better define the mechanisms controlling this remarkable switch in SSC potential.     

Juho joined the Hobbs lab in late 2013. Building on a collaboration formed during Juho’s PhD studies at Finland’s University of Turku and when Robin was at the Beth Israel Deaconess Medical Center linked to Harvard Medical School in Boston; Juho was able to secure a prestigious Fellowship from the Sigrid Jusélius Foundation to allow him to pursue his research interests and join Robin’s newly established Germline Stem Cell Laboratory at ARMI. 

Since joining ARMI, Juho has taken advantage of the dynamic scientific environment and excellent research facilities of the institute to further his interest in SSC biology and regenerative medicine. He has also been able to attend many of Stem Cells Australia’s scientific meetings and looks forward to further collaboration with researchers in the Pluripotency and Reprogramming theme.

Commenting on his interest Juho said,“Testes are an ideal tissue in which to study the properties of adult stem cells. SSCs reside on the basement membrane of the seminiferous tubules in the testis, which enables convenient monitoring and imaging of events in the stem cell pool plus subsequent SSC isolation. Further, SSCs can be cultured long-term within the laboratory, allowing extensive expansion of SSC populations for experimental analysis.”

Since joining the Hobbs group, Juho has become increasingly interested in the functional heterogeneity of cells within SSC cultures and how this relates to their capability of generating embryonic-like stem cells. “Within the testis, SSCs only generate sperm, however when grown in the laboratory SSCs sometimes generate pluripotent stem cells that are capable of producing any cell type within the body,” says Juho. 

However, this SSC reprogramming phenomenon is poorly understood and takes place at a low frequency and in an unpredictable manner. Interestingly, SSCs express a number of genes associated with early embryonic development and pluripotent stem cells including Oct4, Lin28 and Sall4. Given that discrete subsets of SSCs display elevated expression of these embryonic factors, some SSC subpopulations may be more prone to undergo transformation to pluripotent stem cells than others. By taking advantage of a variety of mouse models and gene deletion approaches Juho aims to define the functional differences between these subpopulations and the regulation of pluripotency-associated gene expression in SSCs.

“A better understanding of the functional relevance of embryonic stem cell genes in SSCs may help us to control the reprogramming process,” says Juho. “SSCs are considered a promising alternative source of pluripotent cells for regenerative medicine.”

Stem Cells Australia is delighted to welcome Robin Hobbs and his team to our network and look forward to learning what they can reveal about the fascinating stem cells of the testis.