Mitochondrial Dynamics Is Critical for the Full Pluripotency and Embryonic Developmental Potential of Pluripotent Stem Cells

被引：93

作者：

Zhong, Xiuying ^{[1
,2
,3
,4
]}

Cui, Peng ^{[5
]}

Cai, Yongping ^{[6
]}

Wang, Lihua ^{[4
]}

He, Xiaoping ^{[4
]}

Long, Peipei ^{[5
]}

Lu, Kangyang ^{[6
]}

Yan, Ronghui ^{[1
,2
,4
,7
,8
]}

Zhang, Ying ^{[5
]}

Pan, Xin ^{[9
]}

Zhao, Xiaoyang ^{[5
]}

Li, Wei ^{[5
]}

Zhang, Huafeng ^{[4
]}

Zhou, Qi ^{[5
]}

Gao, Ping ^{[1
,2
,3
,4
,7
,8
,10
]}

机构：

[1] South China Univ Technol, Guangzhou Peoples Hosp 1, Sch Med, Guangzhou 510006, Guangdong, Peoples R China

[2] South China Univ Technol, Inst Life Sci, Guangzhou 510006, Guangdong, Peoples R China

[3] South China Univ Technol, Natl Engn Res Ctr Tissue Restorat & Reconstruct, Guangzhou 510006, Guangdong, Peoples R China

[4] Univ Sci & Technol China, Sch Life Sci, CAS Key Lab Innate Immun & Chron Dis, Div Mol Med,Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China

[5] Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, Beijing 100101, Peoples R China

[6] Anhui Med Univ, Sch Med, Dept Pathol, Hefei 230022, Anhui, Peoples R China

[7] South China Univ Technol, Key Lab Biomed Engn Guangdong Prov, Guangzhou 510006, Guangdong, Peoples R China

[8] South China Univ Technol, Minist Educ, Key Lab Biomed Mat & Engn, Guangzhou 510006, Guangdong, Peoples R China

[9] Natl Ctr Biomed Anal, Inst Basic Med Sci, Beijing 100853, Peoples R China

[10] Guangzhou Regenerat Med & Hlth Guangdong Lab, Guangzhou 510005, Guangdong, Peoples R China

来源：

CELL METABOLISM | 2019年 / 29卷 / 04期

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

BETA-CATENIN; GLYCOLYTIC METABOLISM; FATE DECISIONS; GROUND-STATE; DIFFERENTIATION; FUSION; FIBROBLASTS; FISSION; MICE;

D O I：

10.1016/j.cmet.2018.11.007

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

While the pluripotency of stem cells is known to determine the fate of embryonic development, the mechanisms underlying the acquisition and maintenance of full pluripotency largely remain elusive. Here, we show that the balance between mitochondrial fission and fusion is critical for the full pluripotency of stem cells. By analyzing induced pluripotent stem cells with differential developmental potential, we found that excess mitochondrial fission is associated with an impaired embryonic developmental potential. We further uncover that the disruption of mitochondrial dynamics impairs the differentiation and embryonic development of pluripotent stem cells; most notably, pluripotent stem cells that display excess mitochondrial fission fail to produce live-born offspring by tetraploid complementation. Mechanistically, excess mitochondrial fission increases cytosolic Ca2+ entry and CaMKII activity, leading to ubiquitin-mediated proteasomal degradation of beta-Catenin protein. Our results reveal a previously unappreciated fundamental role for mitochondrial dynamics in determining the full pluripotency and embryonic developmental potential of pluripotent stem cells.

引用

页码：979 / +

页数：18

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