A1 Refereed original research article in a scientific journal
Identification of dynamic undifferentiated cell states within the male germline
Authors: 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
Publisher: NATURE PUBLISHING GROUP
Publication year: 2018
Journal: Nature Communications
Journal name in source: NATURE COMMUNICATIONS
Journal acronym: NAT COMMUN
Article number: 2819
Volume: 9
Number of pages: 18
ISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-018-04827-z
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/35443179
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 (A(undiff)); however, only a fraction of this population act as stem cells in undisturbed testis and A(undiff) 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 A(undiff) 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.
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