Telomere-dependent and telomere-independent roles of RAP1 in regulating human stem cell homeostasis.
10.1007/s13238-019-0610-7
- Author:
Xing ZHANG
1
;
Zunpeng LIU
1
;
Xiaoqian LIU
1
;
Si WANG
2
;
Yiyuan ZHANG
3
;
Xiaojuan HE
2
;
Shuhui SUN
3
;
Shuai MA
3
;
Ng SHYH-CHANG
1
;
Feng LIU
4
;
Qiang WANG
4
;
Xiaoqun WANG
3
;
Lin LIU
5
;
Weiqi ZHANG
6
;
Moshi SONG
7
;
Guang-Hui LIU
8
;
Jing QU
9
Author Information
1. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
2. Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing, 100053, China.
3. National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
4. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
5. State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.
6. Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing, 100053, China. weiqizhang@aliyun.com.
7. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. songmoshi@ioz.ac.cn.
8. Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing, 100053, China. ghliu@ibp.ac.cn.
9. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. qujing@ioz.ac.cn.
- Publication Type:Journal Article
- Keywords:
RAP1;
RELN;
methylation;
stem cell;
telomere
- From:
Protein & Cell
2019;10(9):649-667
- CountryChina
- Language:English
-
Abstract:
RAP1 is a well-known telomere-binding protein, but its functions in human stem cells have remained unclear. Here we generated RAP1-deficient human embryonic stem cells (hESCs) by using CRISPR/Cas9 technique and obtained RAP1-deficient human mesenchymal stem cells (hMSCs) and neural stem cells (hNSCs) via directed differentiation. In both hMSCs and hNSCs, RAP1 not only negatively regulated telomere length but also acted as a transcriptional regulator of RELN by tuning the methylation status of its gene promoter. RAP1 deficiency enhanced self-renewal and delayed senescence in hMSCs, but not in hNSCs, suggesting complicated lineage-specific effects of RAP1 in adult stem cells. Altogether, these results demonstrate for the first time that RAP1 plays both telomeric and nontelomeric roles in regulating human stem cell homeostasis.
