High Canonical Wnt/β-Catenin Activity Sensitizes Murine Hematopoietic Stem and Progenitor Cells to DNA Damage

被引：3
作者：
Wang, Yiting [1 ]
Cui, Hui [2 ,3 ]
Tao, Si [2 ,3 ]
Zeng, Ting [2 ,3 ]
Wu, Jianying [2 ,3 ]
Tao, Zhendong [4 ]
Zhang, Liu [5 ]
Zou, Bing [2 ,3 ]
Chen, Zhiyang [6 ]
Garside, George B. [7 ]
Tang, Duozhuang [1 ]
机构：
[1] Nanchang Univ, Dept Hematol, Affiliated Hosp 2, Min De Rd 1, Nanchang 330006, Jiangxi, Peoples R China
[2] Nanchang Univ, Dept Oncol, Jiangxi Key Lab Clin & Translat Canc Res, Affiliated Hosp 2, Nanchang, Jiangxi, Peoples R China
[3] Nanchang Univ, Dept Oncol, Affiliated Hosp 2, Nanchang, Jiangxi, Peoples R China
[4] Jiangxi Prov Hosp Integrated Chinese & Western Me, Dept Med Lab Med, Nanchang, Jiangxi, Peoples R China
[5] Peking Univ, Intens Care Unit, Peoples Hosp, Beijing, Peoples R China
[6] Jinan Univ, Minist Educ, Key Lab Regenerat Med, Guangzhou, Guangdong, Peoples R China
[7] Fritz Lipmann Inst, Leibniz Inst Aging, Jena, Germany
来源：
STEM CELL REVIEWS AND REPORTS | 2020年 / 16卷 / 01期
关键词：
Wnt; Hematopoietic stem cells; Hematopoietic progenitor cells; DNA damage; BETA-CATENIN; SELF-RENEWAL; INTESTINAL STEM; MOUSE; DIFFERENTIATION; IMPAIRS; CANCER; TUMORIGENESIS; ACCUMULATION; HOMEOSTASIS;
D O I：
10.1007/s12015-019-09930-2
中图分类号：
Q813 [细胞工程];
学科分类号：
摘要：
Aging is characterized by the accumulation of DNA damage and a decrease in stem cell functionality, yet molecular mechanisms that limit the maintenance of stem cells in response to DNA damage remain to be delineated. Here we show in mouse models that DNA damage leads to a transient over-activation of Wnt signaling in hematopoietic stem cells (HSCs), and that high activity of canonical Wnt/beta-catenin signaling sensitizes HSCs to DNA damage induced by X-irradiation which results in preferential maintenance of HSCs with low levels of Wnt signaling. The study shows that genetic or chemical activation of canonical Wnt signaling enhances radiosensitivity of HSCs while inhibition of Wnt signaling decreases it. Together, these results indicate that levels of Wnt signaling activity mediate heterogeneity in the sensitivity of HSCs to DNA damage induced depletion. These findings could be relevant for molecular alterations and selection of stem cells in the context of DNA damage accumulation during aging and cancer formation.
引用
收藏
页码：212 / 221
页数：10
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