Identification of dynamic undifferentiated cell states within the male germline

Research output: Contribution to journalArticleResearchpeer-review

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 languageEnglish
Article number2819
Number of pages18
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 19 Jul 2018

Keywords

  • adult stem cells
  • regeneration
  • stem-cell niche

Cite this

@article{f9dee5051e994db3a5e81fcd57c8b2e0,
title = "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.",
keywords = "adult stem cells, regeneration, stem-cell niche",
author = "La, {Hue M.} and Juho-Antti M{\"a}kel{\"a} and Ai-Leen Chan and Rossello, {Fernando J.} and Nefzger, {Christian M.} and Legrand, {Julien M. D.} and {De Seram}, Mia and Polo, {Jose M.} and Hobbs, {Robin M.}",
year = "2018",
month = "7",
day = "19",
doi = "10.1038/s41467-018-04827-z",
language = "English",
volume = "9",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

Identification of dynamic undifferentiated cell states within the male germline. / La, Hue M.; Mäkelä, Juho-Antti; Chan, Ai-Leen; Rossello, Fernando J.; Nefzger, Christian M.; Legrand, Julien M. D.; De Seram, Mia; Polo, Jose M.; Hobbs, Robin M.

In: Nature Communications, Vol. 9, No. 1, 2819, 19.07.2018.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Identification of dynamic undifferentiated cell states within the male germline

AU - La, Hue M.

AU - Mäkelä, Juho-Antti

AU - Chan, Ai-Leen

AU - Rossello, Fernando J.

AU - Nefzger, Christian M.

AU - Legrand, Julien M. D.

AU - De Seram, Mia

AU - Polo, Jose M.

AU - Hobbs, Robin M.

PY - 2018/7/19

Y1 - 2018/7/19

N2 - 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.

AB - 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.

KW - adult stem cells

KW - regeneration

KW - stem-cell niche

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