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Transcriptome profiling reveals signaling conditions dictating human spermatogonia fate in vitro
Author(s) -
Kun Tan,
H. C. Song,
Merlin Thompson,
Sarah Munyoki,
Meena Sukhwani,
TungChin Hsieh,
Kyle E. Orwig,
Miles Wilkinson
Publication year - 2020
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2000362117
Subject(s) - transcriptome , profiling (computer programming) , computational biology , in vitro , biology , microbiology and biotechnology , gene expression profiling , genetics , computer science , gene , gene expression , operating system
Significance The ability to culture human spermatogonial stem cells (SSCs) in vitro is critical to develop SSC therapeutic approaches to treat male infertility. To achieve this goal, it is important to define molecular pathways in human SSCs. Toward this end, we developed an approach to purify human primitive undifferentiated spermatogonia (uSPG) highly enriched in SSCs. Comparative RNA-sequencing analysis of these primitive uSPG versus differentiating SPG identified differentially expressed genes encoding key components in several signaling pathways. Leveraging this information, coupled with single-cell RNA-sequencing analysis, we studied the effects of modulating signaling pathways on human SPG fate in vitro. Inhibition of AKT signaling favored primitive uSPG fate, which can be applied to culture SSCs for therapeutic applications.

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