| Title | ATF6 safeguards organelle homeostasis and cellular aging in human mesenchymal stem cells |
| Authors | Wang, Si Hu, Boqiang Ding, Zhichao Dang, Yujiao Wu, Jun Li, Di Liu, Xiaoling Xiao, Bailong Zhang, Weiqi Ren, Ruotong Lei, Jinghui Hu, Huifang Chen, Chang Chan, Piu Li, Dong Qu, Jing Tang, Fuchou Liu, Guang-Hui |
| Affiliation | Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, CAS Ctr Excellence Biomacromol, Beijing 100101, Peoples R China. Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, Beijing 100101, Peoples R China. Univ Chinese Acad Sci, Beijing 100049, Peoples R China. Capital Med Univ, Natl Clin Res Ctr Geriatr Disorders, Xuanwu Hosp, Beijing 100053, Peoples R China. Peking Univ, Coll Life Sci, Beijing Adv Innovat Ctr Genom ICG, Beijing 100871, Peoples R China. Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China. Salk Inst Biol Studies, Gene Express Lab, 10010 North Torrey Pines Rd, La Jolla, CA 92037 USA. Tsinghua Univ, Sch Pharmaceut Sci, Tsinghua Peking Joint Ctr Life Sci, IDG McGovern Inst Brain Res, Beijing 100084, Peoples R China. Minist Educ, Key Lab Cell Proliferat & Differentiat, Beijing 100871, Peoples R China. Peking Univ, Biomed Inst Pioneering Invest Via Convergen, Beijing 100871, Peoples R China. Jinan Univ, Key Lab Regenerat Med, Minist Educ, Inst Aging & Regenerat Med, Guangzhou 510632, Guangdong, Peoples R China. Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, CAS Ctr Excellence Biomacromol, Beijing 100101, Peoples R China. Qu, J (reprint author), Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, Beijing 100101, Peoples R China. Qu, J Liu, GH (reprint author), Univ Chinese Acad Sci, Beijing 100049, Peoples R China. Qu, J Liu, GH (reprint author), Capital Med Univ, Natl Clin Res Ctr Geriatr Disorders, Xuanwu Hosp, Beijing 100053, Peoples R China. Tang, FC (reprint author), Peking Univ, Coll Life Sci, Beijing Adv Innovat Ctr Genom ICG, Beijing 100871, Peoples R China. Tang, FC (reprint author), Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China. Tang, FC (reprint author), Minist Educ, Key Lab Cell Proliferat & Differentiat, Beijing 100871, Peoples R China. Tang, FC (reprint author), Peking Univ, Biomed Inst Pioneering Invest Via Convergen, Beijing 100871, Peoples R China. Liu, GH (reprint author), Jinan Univ, Key Lab Regenerat Med, Minist Educ, Inst Aging & Regenerat Med, Guangzhou 510632, Guangdong, Peoples R China. |
| Keywords | UNFOLDED PROTEIN RESPONSE ENDOPLASMIC-RETICULUM STRESS NF-Y CBF ER STRESS C-FOS STRUCTURED ILLUMINATION WERNER SYNDROME LIVE CELLS TRANSCRIPTION ACTIVATION |
| Issue Date | 2018 |
| Publisher | CELL DISCOVERY |
| Citation | CELL DISCOVERY. 2018, 4. |
| Abstract | Loss of organelle homeostasis is a hallmark of aging. However, it remains elusive how this occurs at gene expression level. Here, we report that human mesenchymal stem cell (hMSC) aging is associated with dysfunction of double-membrane organelles and downregulation of transcription factor ATF6. CRISPR/Cas9-mediated inactivation of ATF6 in hMSCs, not in human embryonic stem cells and human adipocytes, results in premature cellular aging, characteristic of loss of endomembrane homeostasis. Transcriptomic analyses uncover cell type-specific constitutive and stress-induced ATF6-regulated genes implicated in various layers of organelles' homeostasis regulation. FOS was characterized as a constitutive ATF6 responsive gene, downregulation of which contributes to hMSC aging. Our study unravels the first ATF6-regulated gene expression network related to homeostatic regulation of membrane organelles, and provides novel mechanistic insights into aging-associated attrition of human stem cells. |
| URI | http://hdl.handle.net/20.500.11897/500032 |
| ISSN | 2056-5968 |
| DOI | 10.1038/s41421-017-0003-0 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 生命科学学院 |
