1.Telomere-dependent and telomere-independent roles of RAP1 in regulating human stem cell homeostasis.
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
Protein & Cell 2019;10(9):649-667
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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