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Stem Cell Reports. 2017 Mar 14;8(3):561-575. doi: 10.1016/j.stemcr.2017.01.006. Epub 2017 Feb 9.

SHISA6 Confers Resistance to Differentiation-Promoting Wnt/β-Catenin Signaling in Mouse Spermatogenic Stem Cells.

Author information

1
Division of Germ Cell Biology, National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki 444-8787, Japan; Department of Basic Biology, School of Life Science, Graduate University for Advanced Studies (Sokendai), Okazaki 444-8585, Japan.
2
Laborarory Animal Resource Center, University of Tsukuba, Tsukuba 305-8575, Japan.
3
Division of Morphogenesis, National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki 444-8585, Japan.
4
Division of Molecular and Developmental Biology, National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki 444-8787, Japan; Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki 444-8787, Japan.
5
Division of Developmental Genetics, National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki 444-8787, Japan.
6
Division of Germ Cell Biology, National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki 444-8787, Japan; Department of Basic Biology, School of Life Science, Graduate University for Advanced Studies (Sokendai), Okazaki 444-8585, Japan; Laboratory of Animal Reproduction and Development, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan.
7
Division of Germ Cell Biology, National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki 444-8787, Japan.
8
Laboratory of Proteomics, Institute of Molecular Medicine and Life Science, Yokohama City University Association of Medical Science, Yokohama 236-0004, Japan.
9
Division of Experimental Therapeutics Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
10
Department of Basic Biology, School of Life Science, Graduate University for Advanced Studies (Sokendai), Okazaki 444-8585, Japan; Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki 444-8787, Japan; Division of Developmental Genetics, National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki 444-8787, Japan; Life Science Center of Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba 305-8577, Japan.
11
Department of Basic Biology, School of Life Science, Graduate University for Advanced Studies (Sokendai), Okazaki 444-8585, Japan; Division of Morphogenesis, National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki 444-8585, Japan.
12
Laborarory Animal Resource Center, University of Tsukuba, Tsukuba 305-8575, Japan; Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
13
Department of Basic Biology, School of Life Science, Graduate University for Advanced Studies (Sokendai), Okazaki 444-8585, Japan; Division of Molecular and Developmental Biology, National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki 444-8787, Japan; Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki 444-8787, Japan.
14
Division of Germ Cell Biology, National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki 444-8787, Japan; Department of Basic Biology, School of Life Science, Graduate University for Advanced Studies (Sokendai), Okazaki 444-8585, Japan. Electronic address: shosei@nibb.ac.jp.

Abstract

In the seminiferous tubules of mouse testes, a population of glial cell line-derived neurotrophic factor family receptor alpha 1 (GFRα1)-positive spermatogonia harbors the stem cell functionality and supports continual spermatogenesis, likely independent of asymmetric division or definitive niche control. Here, we show that activation of Wnt/β-catenin signaling promotes spermatogonial differentiation and reduces the GFRα1+ cell pool. We further discovered that SHISA6 is a cell-autonomous Wnt inhibitor that is expressed in a restricted subset of GFRα1+ cells and confers resistance to the Wnt/β-catenin signaling. Shisa6+ cells appear to show stem cell-related characteristics, conjectured from the morphology and long-term fates of T (Brachyury)+ cells that are found largely overlapped with Shisa6+ cells. This study proposes a generic mechanism of stem cell regulation in a facultative (or open) niche environment, with which different levels of a cell-autonomous inhibitor (SHISA6, in this case) generates heterogeneous resistance to widely distributed differentiation-promoting extracellular signaling, such as WNTs.

KEYWORDS:

Shisa6; Wnt/β-catenin inhibitor; differentiation; mouse spermatogenesis; stem cell

PMID:
28196692
PMCID:
PMC5355566
DOI:
10.1016/j.stemcr.2017.01.006
[Indexed for MEDLINE]
Free PMC Article

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