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Identification of dynamic undifferentiated cell states within the male germline.

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.

SUBMITTER: La HM

PROVIDER: S-EPMC6053434 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Identification of dynamic undifferentiated cell states within the male germline.

La Hue M HM Mäkelä Juho-Antti JA Chan Ai-Leen AL Rossello Fernando J FJ Nefzger Christian M CM Legrand Julien M D JMD De Seram Mia M Polo Jose M JM Hobbs Robin M RM

Nature communications 20180719 1

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<sub>undiff</sub>); however, only a fraction of this population act as stem cells in undisturbed testis and A<sub>undiff</sub> hierarchy remains contentious. Through newly developed compound reporter mice, here we define molecular signatures of self-renewin ...[more]

PMID: 30026551

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Dataset Information

Identification of dynamic undifferentiated cell states within the male germline.

Publications

Identification of dynamic undifferentiated cell states within the male germline.

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