期刊
PROTEIN & CELL
卷 10, 期 9, 页码 649-667出版社
SPRINGEROPEN
DOI: 10.1007/s13238-019-0610-7
关键词
RAP1; stem cell; telomere; RELN; methylation
类别
资金
- National Key Research and Development Program of China [2018YFA0107001, 2018YFC2000100, 2018YFA0107203, 2017YFA0103304, 2017 YFA0102802, 2015CB964800, 2014CB910503]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA16010100]
- National Natural Science Foundation of China [81625009, 81330008, 91749202, 91749123, 31671429, 81671377, 81771515, 31601109, 31601158, 81701388, 81422017, 81601233, 81471414, 81870228, 81822018, 81801399, 31801010, 81801370, 81861168034]
- Program of Beijing Municipal Science and Technology Commission [Z151100003915072]
- Key Research Program of the Chinese Academy of Sciences [KJZDEWTZ-L05]
- Beijing Municipal Commission of Health and Family Planning [PXM2018_026283_ 000002]
- Advanced Innovation Center for Human Brain Protection [117212]
- State Key Laboratory of Membrane Biology
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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