DNMT3L promotes quiescence in postnatal spermatogonial progenitor cells

Hung Fu Liao, Wendy S C Chen, Yu Hsiang Chen, Tzu Hao Kao, Yen Tzu Tseng, Chien Yueh Lee, Yu Chiao Chiu, Pei Lung Lee, Qian Jia Lin, Yung Hao Ching, Kenichiro Hata, Winston T K Cheng, Mong Hsun Tsai, Hiroyuki Sasaki, Hong Nerng Ho, Shinn Chih Wu, Yen-Hua Huang, Pauline Yen, Shau Ping Lin

研究成果: 雜誌貢獻文章

25 引文 (Scopus)

摘要

The ability of adult stem cells to reside in a quiescent state is crucial for preventing premature exhaustion of the stem cell pool. However, the intrinsic epigenetic factors that regulate spermatogonial stem cell quiescence are largely unknown. Here, we investigate in mice how DNA methyltransferase 3-like (DNMT3L), an epigenetic regulator important for interpreting chromatin context and facilitating de novo DNA methylation, sustains the long-term male germ cell pool. We demonstrated that stem cell-enriched THY1+ spermatogonial stem/ progenitor cells (SPCs) constituted a DNMT3L-expressing population in postnatal testes. DNMT3L influenced the stability of promyelocytic leukemia zinc finger (PLZF), potentially by downregulating Cdk2/CDK2 expression, which sequestered CDK2-mediated PLZF degradation. Reduced PLZF in Dnmt3l KO THY1+ cells released its antagonist, Sallike protein 4A (SALL4A), which is associated with overactivated ERK and AKT signaling cascades. Furthermore, DNMT3L was required to suppressthe cell proliferation-promoting factor SALL4B in THY1+ SPCs and to prevent premature stem cell exhaustion. Our results indicate that DNMT3L is required to delicately balance the cycling and quiescence of SPCs. These findings reveal a novel role for DNMT3L in modulating postnatal SPC cell fate decisions.
原文英語
頁(從 - 到)2402-2413
頁數12
期刊Development
141
發行號12
DOIs
出版狀態已發佈 - 2014

指紋

Methyltransferases
Stem Cells
DNA
Zinc Fingers
Leukemia
Epigenomics
Adult Germline Stem Cells
Intrinsic Factor
Adult Stem Cells
DNA Methylation
Germ Cells
Chromatin
Testis
Down-Regulation
Cell Proliferation

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

引用此文

Liao, H. F., Chen, W. S. C., Chen, Y. H., Kao, T. H., Tseng, Y. T., Lee, C. Y., ... Lin, S. P. (2014). DNMT3L promotes quiescence in postnatal spermatogonial progenitor cells. Development, 141(12), 2402-2413. https://doi.org/10.1242/dev.105130

DNMT3L promotes quiescence in postnatal spermatogonial progenitor cells. / Liao, Hung Fu; Chen, Wendy S C; Chen, Yu Hsiang; Kao, Tzu Hao; Tseng, Yen Tzu; Lee, Chien Yueh; Chiu, Yu Chiao; Lee, Pei Lung; Lin, Qian Jia; Ching, Yung Hao; Hata, Kenichiro; Cheng, Winston T K; Tsai, Mong Hsun; Sasaki, Hiroyuki; Ho, Hong Nerng; Wu, Shinn Chih; Huang, Yen-Hua; Yen, Pauline; Lin, Shau Ping.

於: Development, 卷 141, 編號 12, 2014, p. 2402-2413.

研究成果: 雜誌貢獻文章

Liao, HF, Chen, WSC, Chen, YH, Kao, TH, Tseng, YT, Lee, CY, Chiu, YC, Lee, PL, Lin, QJ, Ching, YH, Hata, K, Cheng, WTK, Tsai, MH, Sasaki, H, Ho, HN, Wu, SC, Huang, Y-H, Yen, P & Lin, SP 2014, 'DNMT3L promotes quiescence in postnatal spermatogonial progenitor cells', Development, 卷 141, 編號 12, 頁 2402-2413. https://doi.org/10.1242/dev.105130
Liao HF, Chen WSC, Chen YH, Kao TH, Tseng YT, Lee CY 等. DNMT3L promotes quiescence in postnatal spermatogonial progenitor cells. Development. 2014;141(12):2402-2413. https://doi.org/10.1242/dev.105130
Liao, Hung Fu ; Chen, Wendy S C ; Chen, Yu Hsiang ; Kao, Tzu Hao ; Tseng, Yen Tzu ; Lee, Chien Yueh ; Chiu, Yu Chiao ; Lee, Pei Lung ; Lin, Qian Jia ; Ching, Yung Hao ; Hata, Kenichiro ; Cheng, Winston T K ; Tsai, Mong Hsun ; Sasaki, Hiroyuki ; Ho, Hong Nerng ; Wu, Shinn Chih ; Huang, Yen-Hua ; Yen, Pauline ; Lin, Shau Ping. / DNMT3L promotes quiescence in postnatal spermatogonial progenitor cells. 於: Development. 2014 ; 卷 141, 編號 12. 頁 2402-2413.
@article{1a40a8fa89f74c59a0e054678673f7d9,
title = "DNMT3L promotes quiescence in postnatal spermatogonial progenitor cells",
abstract = "The ability of adult stem cells to reside in a quiescent state is crucial for preventing premature exhaustion of the stem cell pool. However, the intrinsic epigenetic factors that regulate spermatogonial stem cell quiescence are largely unknown. Here, we investigate in mice how DNA methyltransferase 3-like (DNMT3L), an epigenetic regulator important for interpreting chromatin context and facilitating de novo DNA methylation, sustains the long-term male germ cell pool. We demonstrated that stem cell-enriched THY1+ spermatogonial stem/ progenitor cells (SPCs) constituted a DNMT3L-expressing population in postnatal testes. DNMT3L influenced the stability of promyelocytic leukemia zinc finger (PLZF), potentially by downregulating Cdk2/CDK2 expression, which sequestered CDK2-mediated PLZF degradation. Reduced PLZF in Dnmt3l KO THY1+ cells released its antagonist, Sallike protein 4A (SALL4A), which is associated with overactivated ERK and AKT signaling cascades. Furthermore, DNMT3L was required to suppressthe cell proliferation-promoting factor SALL4B in THY1+ SPCs and to prevent premature stem cell exhaustion. Our results indicate that DNMT3L is required to delicately balance the cycling and quiescence of SPCs. These findings reveal a novel role for DNMT3L in modulating postnatal SPC cell fate decisions.",
keywords = "DNMT3L, Mouse, Proliferation, Quiescence, Spermatogonial progenitor cell",
author = "Liao, {Hung Fu} and Chen, {Wendy S C} and Chen, {Yu Hsiang} and Kao, {Tzu Hao} and Tseng, {Yen Tzu} and Lee, {Chien Yueh} and Chiu, {Yu Chiao} and Lee, {Pei Lung} and Lin, {Qian Jia} and Ching, {Yung Hao} and Kenichiro Hata and Cheng, {Winston T K} and Tsai, {Mong Hsun} and Hiroyuki Sasaki and Ho, {Hong Nerng} and Wu, {Shinn Chih} and Yen-Hua Huang and Pauline Yen and Lin, {Shau Ping}",
year = "2014",
doi = "10.1242/dev.105130",
language = "English",
volume = "141",
pages = "2402--2413",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "12",

}

TY - JOUR

T1 - DNMT3L promotes quiescence in postnatal spermatogonial progenitor cells

AU - Liao, Hung Fu

AU - Chen, Wendy S C

AU - Chen, Yu Hsiang

AU - Kao, Tzu Hao

AU - Tseng, Yen Tzu

AU - Lee, Chien Yueh

AU - Chiu, Yu Chiao

AU - Lee, Pei Lung

AU - Lin, Qian Jia

AU - Ching, Yung Hao

AU - Hata, Kenichiro

AU - Cheng, Winston T K

AU - Tsai, Mong Hsun

AU - Sasaki, Hiroyuki

AU - Ho, Hong Nerng

AU - Wu, Shinn Chih

AU - Huang, Yen-Hua

AU - Yen, Pauline

AU - Lin, Shau Ping

PY - 2014

Y1 - 2014

N2 - The ability of adult stem cells to reside in a quiescent state is crucial for preventing premature exhaustion of the stem cell pool. However, the intrinsic epigenetic factors that regulate spermatogonial stem cell quiescence are largely unknown. Here, we investigate in mice how DNA methyltransferase 3-like (DNMT3L), an epigenetic regulator important for interpreting chromatin context and facilitating de novo DNA methylation, sustains the long-term male germ cell pool. We demonstrated that stem cell-enriched THY1+ spermatogonial stem/ progenitor cells (SPCs) constituted a DNMT3L-expressing population in postnatal testes. DNMT3L influenced the stability of promyelocytic leukemia zinc finger (PLZF), potentially by downregulating Cdk2/CDK2 expression, which sequestered CDK2-mediated PLZF degradation. Reduced PLZF in Dnmt3l KO THY1+ cells released its antagonist, Sallike protein 4A (SALL4A), which is associated with overactivated ERK and AKT signaling cascades. Furthermore, DNMT3L was required to suppressthe cell proliferation-promoting factor SALL4B in THY1+ SPCs and to prevent premature stem cell exhaustion. Our results indicate that DNMT3L is required to delicately balance the cycling and quiescence of SPCs. These findings reveal a novel role for DNMT3L in modulating postnatal SPC cell fate decisions.

AB - The ability of adult stem cells to reside in a quiescent state is crucial for preventing premature exhaustion of the stem cell pool. However, the intrinsic epigenetic factors that regulate spermatogonial stem cell quiescence are largely unknown. Here, we investigate in mice how DNA methyltransferase 3-like (DNMT3L), an epigenetic regulator important for interpreting chromatin context and facilitating de novo DNA methylation, sustains the long-term male germ cell pool. We demonstrated that stem cell-enriched THY1+ spermatogonial stem/ progenitor cells (SPCs) constituted a DNMT3L-expressing population in postnatal testes. DNMT3L influenced the stability of promyelocytic leukemia zinc finger (PLZF), potentially by downregulating Cdk2/CDK2 expression, which sequestered CDK2-mediated PLZF degradation. Reduced PLZF in Dnmt3l KO THY1+ cells released its antagonist, Sallike protein 4A (SALL4A), which is associated with overactivated ERK and AKT signaling cascades. Furthermore, DNMT3L was required to suppressthe cell proliferation-promoting factor SALL4B in THY1+ SPCs and to prevent premature stem cell exhaustion. Our results indicate that DNMT3L is required to delicately balance the cycling and quiescence of SPCs. These findings reveal a novel role for DNMT3L in modulating postnatal SPC cell fate decisions.

KW - DNMT3L

KW - Mouse

KW - Proliferation

KW - Quiescence

KW - Spermatogonial progenitor cell

UR - http://www.scopus.com/inward/record.url?scp=84902202454&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902202454&partnerID=8YFLogxK

U2 - 10.1242/dev.105130

DO - 10.1242/dev.105130

M3 - Article

C2 - 24850856

AN - SCOPUS:84902202454

VL - 141

SP - 2402

EP - 2413

JO - Development (Cambridge)

JF - Development (Cambridge)

SN - 0950-1991

IS - 12

ER -