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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. Telomere-dependent and telomereindependent roles of RAP1 in regulating human stem cell homeostasis[J]. Protein&Cell, 2019, 10(9): 649-667. doi: 10.1007/s13238-019-0610-7
Citation: 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. Telomere-dependent and telomereindependent roles of RAP1 in regulating human stem cell homeostasis[J]. Protein&Cell, 2019, 10(9): 649-667. doi: 10.1007/s13238-019-0610-7
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Telomere-dependent and telomereindependent roles of RAP1 in regulating human stem cell homeostasis

    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.
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