Identification of dynamic undifferentiated cell states within the male germline
Files
(Published version)
Date
2018
Authors
La, H.M.
Mäkelä, J.A.
Chan, A.L.
Rossello, F.J.
Nefzger, C.M.
Legrand, J.M.D.
De Seram, M.
Polo, J.M.
Hobbs, R.M.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Nature Communications, 2018; 9(1):1-18
Statement of Responsibility
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 and Robin M. Hobbs
Conference Name
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.
School/Discipline
Dissertation Note
Provenance
Description
Access Status
Rights
© The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.