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.
Original language | English |
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Article number | 2819 |
Number of pages | 18 |
Journal | Nature Communications |
Volume | 9 |
Issue number | 1 |
DOIs | |
Publication status | Published - 19 Jul 2018 |
Keywords
- adult stem cells
- regeneration
- stem-cell niche
Equipment
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Animal Research Platform (MARP)
Christine Findlay (Manager)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility
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FlowCore
Andrew Fryga (Manager)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility
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Genome Modification Platform
Jeanette Rientjes (Manager)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility