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Identification of dynamic undifferentiated cell states within the male germline

Author

Listed:
  • Hue M. La

    (Australian Regenerative Medicine Institute, Monash University
    Monash University)

  • Juho-Antti Mäkelä

    (Australian Regenerative Medicine Institute, Monash University
    Monash University
    Research Centre for Integrative Physiology and Pharmacology, University of Turku)

  • Ai-Leen Chan

    (Australian Regenerative Medicine Institute, Monash University
    Monash University)

  • Fernando J. Rossello

    (Australian Regenerative Medicine Institute, Monash University
    Monash University)

  • Christian M. Nefzger

    (Australian Regenerative Medicine Institute, Monash University
    Monash University)

  • Julien M. D. Legrand

    (Australian Regenerative Medicine Institute, Monash University
    Monash University)

  • Mia Seram

    (Australian Regenerative Medicine Institute, Monash University
    Monash University)

  • Jose M. Polo

    (Australian Regenerative Medicine Institute, Monash University
    Monash University)

  • Robin M. Hobbs

    (Australian Regenerative Medicine Institute, Monash University
    Monash University)

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.

Suggested Citation

  • Hue M. La & Juho-Antti Mäkelä & Ai-Leen Chan & Fernando J. Rossello & Christian M. Nefzger & Julien M. D. Legrand & Mia Seram & Jose M. Polo & Robin M. Hobbs, 2018. "Identification of dynamic undifferentiated cell states within the male germline," Nature Communications, Nature, vol. 9(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04827-z
    DOI: 10.1038/s41467-018-04827-z
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    Cited by:

    1. Hue M. La & Jinyue Liao & Julien M. D. Legrand & Fernando J. Rossello & Ai-Leen Chan & Vijesh Vaghjiani & Jason E. Cain & Antonella Papa & Tin Lap Lee & Robin M. Hobbs, 2022. "Distinctive molecular features of regenerative stem cells in the damaged male germline," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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