Identification of dynamic undifferentiated cell states within the male germline

Hue M. La, Juho-Antti Mäkelä, Ai-Leen Chan, Fernando J. Rossello, Christian M. Nefzger, Julien M. D. Legrand, Mia Seram, Jose M. Polo and Robin M. Hobbs ()
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Hue M. La: Australian Regenerative Medicine Institute, Monash University
Juho-Antti Mäkelä: Australian Regenerative Medicine Institute, Monash University
Ai-Leen Chan: Australian Regenerative Medicine Institute, Monash University
Fernando J. Rossello: Australian Regenerative Medicine Institute, Monash University
Christian M. Nefzger: Australian Regenerative Medicine Institute, Monash University
Julien M. D. Legrand: Australian Regenerative Medicine Institute, Monash University
Mia Seram: Australian Regenerative Medicine Institute, Monash University
Jose M. Polo: Australian Regenerative Medicine Institute, Monash University
Robin M. Hobbs: Australian Regenerative Medicine Institute, Monash University

Nature Communications, 2018, vol. 9, issue 1, 1-18

Abstract: Abstract The role of stem cells in tissue maintenance is appreciated and hierarchical models of stem cell self-renewal and differentiation often proposed. Stem cell activity in the male germline is restricted to undifferentiated A-type spermatogonia (Aundiff); however, only a fraction of this population act as stem cells in undisturbed testis and Aundiff hierarchy remains contentious. Through newly developed compound reporter mice, here we define molecular signatures of self-renewing and differentiation-primed adult Aundiff fractions and dissect Aundiff heterogeneity by single-cell analysis. We uncover an unappreciated population within the self-renewing Aundiff fraction marked by expression of embryonic patterning genes and homeodomain transcription factor PDX1. Importantly, we find that PDX1 marks a population with potent stem cell capacity unique to mature, homeostatic testis and demonstrate dynamic interconversion between PDX1+ and PDX1− Aundiff states upon transplant and culture. We conclude that Aundiff exist in a series of dynamic cell states with distinct function and provide evidence that stability of such states is dictated by niche-derived cues.

Date: 2018
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DOI: 10.1038/s41467-018-04827-z

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