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

Moe Tokue; Kanako Ikami; Seiya Mizuno; Chiyo Takagi; Asuka Miyagi; Ritsuko Takada; Chiyo Noda; Yu Kitadate; Kenshiro Hara; Hiroko Mizuguchi; Takuya Sato; Makoto Mark Taketo; Fumihiro Sugiyama; Takehiko Ogawa; Satoru Kobayashi; Naoto Ueno; Satoru Takahashi; Shinji Takada; Shosei Yoshida

doi:10.1016/j.stemcr.2017.01.006

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

Moe Tokue, Kanako Ikami, Seiya Mizuno, Chiyo Takagi, Asuka Miyagi, Ritsuko Takada, Chiyo Noda, Yu Kitadate, Kenshiro Hara, Hiroko Mizuguchi, Takuya Sato, Makoto Mark Taketo, Fumihiro Sugiyama, Takehiko Ogawa, Satoru Kobayashi, Naoto Ueno, Satoru Takahashi, Shinji Takada, Shosei Yoshida

Research output: Contribution to journal › Article › peer-review

58 Citations (Scopus)

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.

Original language	English
Pages (from-to)	561-575
Number of pages	15
Journal	Stem Cell Reports
Volume	8
Issue number	3
DOIs	https://doi.org/10.1016/j.stemcr.2017.01.006
Publication status	Published - 2017 Mar 14

Keywords

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

ASJC Scopus subject areas

Biochemistry
Genetics
Developmental Biology
Cell Biology

Access to Document

10.1016/j.stemcr.2017.01.006

Cite this

Tokue, M., Ikami, K., Mizuno, S., Takagi, C., Miyagi, A., Takada, R., Noda, C., Kitadate, Y., Hara, K., Mizuguchi, H., Sato, T., Taketo, M. M., Sugiyama, F., Ogawa, T., Kobayashi, S., Ueno, N., Takahashi, S., Takada, S., & Yoshida, S. (2017). SHISA6 Confers Resistance to Differentiation-Promoting Wnt/β-Catenin Signaling in Mouse Spermatogenic Stem Cells. Stem Cell Reports, 8(3), 561-575. https://doi.org/10.1016/j.stemcr.2017.01.006

Tokue, M, Ikami, K, Mizuno, S, Takagi, C, Miyagi, A, Takada, R, Noda, C, Kitadate, Y, Hara, K, Mizuguchi, H, Sato, T, Taketo, MM, Sugiyama, F, Ogawa, T, Kobayashi, S, Ueno, N, Takahashi, S, Takada, S & Yoshida, S 2017, 'SHISA6 Confers Resistance to Differentiation-Promoting Wnt/β-Catenin Signaling in Mouse Spermatogenic Stem Cells', Stem Cell Reports, vol. 8, no. 3, pp. 561-575. https://doi.org/10.1016/j.stemcr.2017.01.006

@article{dba31e9f68ca4183b7eb7626765d7a49,

title = "SHISA6 Confers Resistance to Differentiation-Promoting Wnt/β-Catenin Signaling in Mouse Spermatogenic Stem Cells",

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",

author = "Moe Tokue and Kanako Ikami and Seiya Mizuno and Chiyo Takagi and Asuka Miyagi and Ritsuko Takada and Chiyo Noda and Yu Kitadate and Kenshiro Hara and Hiroko Mizuguchi and Takuya Sato and Taketo, {Makoto Mark} and Fumihiro Sugiyama and Takehiko Ogawa and Satoru Kobayashi and Naoto Ueno and Satoru Takahashi and Shinji Takada and Shosei Yoshida",

note = "Publisher Copyright: {\textcopyright} 2017 The Authors",

year = "2017",

month = mar,

day = "14",

doi = "10.1016/j.stemcr.2017.01.006",

language = "English",

volume = "8",

pages = "561--575",

journal = "Stem Cell Reports",

issn = "2213-6711",

publisher = "Cell Press",

number = "3",

}

TY - JOUR

T1 - SHISA6 Confers Resistance to Differentiation-Promoting Wnt/β-Catenin Signaling in Mouse Spermatogenic Stem Cells

AU - Tokue, Moe

AU - Ikami, Kanako

AU - Mizuno, Seiya

AU - Takagi, Chiyo

AU - Miyagi, Asuka

AU - Takada, Ritsuko

AU - Noda, Chiyo

AU - Kitadate, Yu

AU - Hara, Kenshiro

AU - Mizuguchi, Hiroko

AU - Sato, Takuya

AU - Taketo, Makoto Mark

AU - Sugiyama, Fumihiro

AU - Ogawa, Takehiko

AU - Kobayashi, Satoru

AU - Ueno, Naoto

AU - Takahashi, Satoru

AU - Takada, Shinji

AU - Yoshida, Shosei

PY - 2017/3/14

Y1 - 2017/3/14

N2 - 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.

AB - 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.

KW - Shisa6

KW - Wnt/β-catenin inhibitor

KW - differentiation

KW - mouse spermatogenesis

KW - stem cell

UR - http://www.scopus.com/inward/record.url?scp=85012885909&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85012885909&partnerID=8YFLogxK

U2 - 10.1016/j.stemcr.2017.01.006

DO - 10.1016/j.stemcr.2017.01.006

M3 - Article

C2 - 28196692

AN - SCOPUS:85012885909

SN - 2213-6711

VL - 8

SP - 561

EP - 575

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 3

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this