Telomere-dependent and telomereindependent roles of RAP1 in regulating human stem cell homeostasis

doi:10.1007/s13238-019-0610-7

Protein Cell

2019, Vol. 10

Issue (9) : 649-667 https://doi.org/10.1007/s13238-019-0610-7

RESEARCH ARTICLE

Telomere-dependent and telomereindependent roles of RAP1 in regulating human stem cell homeostasis

Xing Zhang^1,^2,⁶, Zunpeng Liu^1,⁶, Xiaoqian Liu¹, Si Wang^2,^3,⁷, Yiyuan Zhang^3,⁶, Xiaojuan He², Shuhui Sun³, Shuai Ma³, Ng Shyh-Chang^1,^6,⁷, Feng Liu^5,^6,⁷, Qiang Wang^5,^6,⁷, Xiaoqun Wang^3,^6,⁷, Lin Liu⁴, Weiqi Zhang^2,^3,^6,⁷(

), Moshi Song^5,^6,⁷(

), Guang-Hui Liu^2,^3,^6,^7,^8,⁹(

), Jing Qu^1,^6,⁷(

)

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 Medicinal Chemical Biology, Nankai University, Tianjin 300071, China
⁵. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
⁶. University of Chinese Academy of Sciences, Beijing 100049, China
⁷. Institute for Stem cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China
⁸. Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou 510632, China
⁹. Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China

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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 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.

Keywords RAP1 stem cell telomere RELN methylation

Corresponding Author(s): Weiqi Zhang,Moshi Song,Guang-Hui Liu,Jing Qu

Issue Date: 24 September 2019

Cite this article:

Xing Zhang,Zunpeng Liu,Xiaoqian Liu, et al. Telomere-dependent and telomereindependent roles of RAP1 in regulating human stem cell homeostasis[J]. Protein Cell, 2019, 10(9): 649-667.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-019-0610-7
https://academic.hep.com.cn/pac/EN/Y2019/V10/I9/649

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