Indirect effects of Wnt3a/β-catenin signalling support mouse spermatogonial stem cells in vitro

Autor: Xiangfan Zhang, Jonathan R. Yeh, Makoto C. Nagano
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Male
Mouse
Cellular differentiation
lcsh:Medicine
Fibroblast growth factor
Cell Fate Determination
Mice
0302 clinical medicine
Molecular Cell Biology
Stem Cell Niche
lcsh:Science
beta Catenin
WNT Signaling Cascade
0303 health sciences
Multidisciplinary
Stem Cells
Wnt signaling pathway
Cell Differentiation
Animal Models
Signaling Cascades
Cell biology
Adult Stem Cells
medicine.anatomical_structure
030220 oncology & carcinogenesis
Medicine
Cellular Types
Stem cell
Cell Division
Germ cell
Signal Transduction
Research Article
endocrine system
Urology
In Vitro Techniques
Biology
Cell Growth
03 medical and health sciences
Paracrine signalling
Model Organisms
Wnt3A Protein
medicine
Animals
Progenitor cell
030304 developmental biology
lcsh:R
Spermatogonia
Germ Cells
Cell culture
Infertility
Immunology
lcsh:Q
Developmental Biology
Zdroj: PLoS ONE, Vol 7, Iss 6, p e40002 (2012)
PLoS ONE
ISSN: 1932-6203
Popis: Proper regulation of spermatogonial stem cells (SSCs) is crucial for sustaining steady-state spermatogenesis. Previous work has identified several paracrine factors involved in this regulation, in particular, glial cell line-derived neurotrophic factor and fibroblast growth factor 2, which promote long-term SSC self-renewal. Using a SSC culture system, we have recently reported that Wnt5a promotes SSC self-renewal through a β-catenin-independent Wnt mechanism whereas the β-catenin-dependent Wnt pathway is not active in SSCs. In contrast, another study has reported that Wnt3a promotes SSC self-renewal through the β-catenin-dependent pathway, as it can stimulate the proliferation of a spermatogonia cell line. To reconcile these two contradictory reports, we assessed Wnt3a effects on SSCs and progenitor cells, rather than a cell line, in vitro. We observed that Wnt3a induced β-catenin-dependent signalling in a large subset of germ cells and increased SSC numbers. However, further investigation revealed that cell populations with greater β-catenin-signalling activity contained fewer SSCs. The increased maintenance of SSCs by Wnt3a coincided with more active cell cycling and the formation of germ cell aggregates, or communities, under feeder-free conditions. Therefore, the results of this study suggest that Wnt3a selectively stimulates proliferation of progenitors that are committed to differentiation or are in the process of exiting the SSC state, leading to enhanced formation of germ cell communities, which indirectly support SSCs and act as an in vitro niche.
Databáze: OpenAIRE
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