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

Protein & Cell
Xing ZhangJing Qu

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.

References

Jun 1, 1991·Current Opinion in Cell Biology·C W Greider
Sep 27, 2001·Cell·E H Blackburn
Nov 2, 2001·Molecular and Cellular Biology·P Moretti, D Shore
May 10, 2002·Nucleic Acids Research·Richard M Cawthon
Jul 29, 2003·Aging Cell·Carole J Proctor, Thomas B L Kirkwood
Oct 21, 2003·Molecular Biology of the Cell·Bibo Li, Titia de Lange
Apr 22, 2004·The Journal of Biological Chemistry·Matthew S O'ConnorZhou Songyang
Jun 11, 2004·Annual Review of Biochemistry·Agata Smogorzewska, Titia de Lange
Sep 3, 2004·Cancer Letters·J Arturo Londoño-Vallejo
Nov 22, 2007·Science·Junying YuJames A Thomson
Jun 7, 2008·Cancer Biology & Therapy·Noriyuki OmuraMichael Goggins
Jun 10, 2008·Nature Protocols·John Arne Dahl, Philippe Collas
Aug 6, 2008·Annual Review of Genetics·Wilhelm Palm, Titia de Lange
Oct 3, 2008·Genome Biology·Huawei XinZhou Songyang
May 26, 2009·Nucleic Acids Research·Jing ChenAnil G Jegga
Feb 25, 2011·Nature·Guang-Hui LiuJuan Carlos Izpisua Belmonte
Mar 23, 2011·Cell Research·Dong YangZhou Songyang
May 26, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Audrey VincentMichael Goggins
Mar 6, 2012·Nature Methods·Ben Langmead, Steven L Salzberg
Aug 28, 2012·Nature Structural & Molecular Biology·Nausica ArnoultAnabelle Decottignies
Mar 19, 2013·PLoS Computational Biology·Ekta KhuranaMark Gerstein
Jun 12, 2013·Cell·Carlos López-OtínGuido Kroemer
Jul 23, 2013·Cell Death & Disease·T Di PalmaM Zannini
Aug 21, 2013·Seminars in Hematology·Rodrigo T Calado, Bogdan Dumitriu
Sep 3, 2013·Nature·Madeline A LancasterJuergen A Knoblich
Jun 28, 2014·Neuroscience Research·Katsutoshi SekineKazunori Nakajima
Jul 1, 2014·Current Pharmaceutical Design·Roger R Reddel
Jul 8, 2014·Nature Communications·Guang-Hui LiuJuan Carlos Izpisua Belmonte
Sep 5, 2014·Nature Protocols·Madeline A Lancaster, Juergen A Knoblich
Sep 28, 2014·Bioinformatics·Simon AndersWolfgang Huber

❮ Previous
Next ❯

Citations

May 20, 2020·Nucleic Acids Research·Huifang HuJing Qu
Aug 12, 2020·Protein & Cell·Yingfeng ZhengWenru Su
May 24, 2020·The Journal of Biological Chemistry·Soujanya VinayagamurthyShantanu Chowdhury
Feb 1, 2020·Cell·Si WangGuang-Hui Liu
Mar 12, 2021·Nucleic Acids Research·Zhiqing DiaoJing Qu
May 20, 2021·Biological Chemistry·Claus KordesDieter Häussinger

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
reverse transcription PCR
Flow cytometry
chromosomal aberrations
immunoprecipitation
ChIP-PCR
RNA-seq
ChIP
electrophoresis
Assay

Software Mentioned

- Pad Prism
hisat2
Graph
ImageJ
Image J
bowtie2
DESeq2 R package
HMMcopy
Image Lab
FlowJo

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.