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 De Seram, Jose M. Polo, Robin M. Hobbs

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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.
Original languageEnglish
Article number2819
Number of pages18
JournalNature Communications
Issue number1
Publication statusPublished - 19 Jul 2018


  • adult stem cells
  • regeneration
  • stem-cell niche

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