%A Xing Zhang, Zunpeng Liu, Xiaoqian Liu, Si Wang, Yiyuan Zhang, Xiaojuan He, Shuhui Sun, Shuai Ma, Ng Shyh-Chang, Feng Liu, Qiang Wang, Xiaoqun Wang, Lin Liu, Weiqi Zhang, Moshi Song, Guang-Hui Liu, Jing Qu %T Telomere-dependent and telomereindependent roles of RAP1 in regulating human stem cell homeostasis %0 Journal Article %D 2019 %J Protein Cell %J Protein & Cell %@ 1674-800X %R 10.1007/s13238-019-0610-7 %P 649-667 %V 10 %N 9 %U {https://journal.hep.com.cn/pac/EN/10.1007/s13238-019-0610-7 %8 2019-09-15 %X

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 direc- ted 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 defi- ciency 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.