PMID- 32698871
OWN - NLM
STAT- MEDLINE
DCOM- 20210618
LR  - 20220531
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 11
IP  - 1
DP  - 2020 Jul 22
TI  - METTL1-mediated m(7)G methylation maintains pluripotency in human stem cells and 
      limits mesoderm differentiation and vascular development.
PG  - 306
LID - 10.1186/s13287-020-01814-4 [doi]
LID - 306
AB  - BACKGROUND: 7-Methylguanosine (m(7)G) is one of the most conserved modifications 
      in nucleosides within tRNAs and rRNAs. It plays essential roles in the regulation 
      of mRNA export, splicing, and translation. Recent studies highlighted the 
      importance of METTL1-mediated m(7)G tRNA methylome in the self-renewal of mouse 
      embryonic stem cells (mESCs) through its ability to regulate mRNA translation. 
      However, the exact mechanisms by which METTL1 regulates pluripotency and 
      differentiation in human induced pluripotent stem cells (hiPSCs) remain unknown. 
      In this study, we evaluated the functions and underlying molecular mechanisms of 
      METTL1 in regulating hiPSC self-renewal and differentiation in vivo and in vitro. 
      METHODS: By establishing METTL1 knockdown (KD) hiPSCs, gene expression profiling 
      was performed by RNA sequencing followed by pathway analyses. Anti-m(7)G 
      northwestern assay was used to identify m(7)G modifications in tRNAs and mRNAs. 
      Polysome profiling was used to assess the translation efficiency of the major 
      pluripotent transcription factors. Moreover, the in vitro and in vivo 
      differentiation capacities of METTL1-KD hiPSCs were assessed in embryoid body 
      (EB) formation and teratoma formation assays. RESULTS: METTL1 silencing resulted 
      in alterations in the global m(7)G profile in hiPSCs and reduced the 
      translational efficiency of stem cell marker genes. METTL1-KD hiPSCs exhibited 
      reduced pluripotency with slower cell cycling. Moreover, METTL1 silencing 
      accelerates hiPSC differentiation into EBs and promotes the expression of 
      mesoderm-related genes. Similarly, METTL1 knockdown enhances teratoma formation 
      and mesoderm differentiation in vivo by promoting cell proliferation and 
      angiogenesis in nude mice. CONCLUSION: Our findings provided novel insight into 
      the critical role of METTL1-mediated m(7)G modification in the regulation of 
      hiPSC pluripotency and differentiation, as well as its potential roles in 
      vascular development and the treatment of vascular diseases.
FAU - Deng, Yujie
AU  - Deng Y
AD  - Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, 510080, China.
AD  - Department of Rehabilitation Medicine, The Sixth Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, 510000, China.
FAU - Zhou, Zhongyang
AU  - Zhou Z
AD  - Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, 510080, China.
FAU - Ji, Weidong
AU  - Ji W
AD  - Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, 510080, China.
FAU - Lin, Shuibin
AU  - Lin S
AD  - Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, 510080, China. linshb6@mail.sysu.edu.cn.
FAU - Wang, Min
AU  - Wang M
AD  - Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, 510080, China. mikewang388@foxmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200722
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
RN  - EC 2.1.1.- (METTL1 protein, human)
RN  - EC 2.1.1.- (Methyltransferases)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Humans
MH  - *Induced Pluripotent Stem Cells/metabolism
MH  - Mesoderm/metabolism
MH  - Methylation
MH  - Methyltransferases/genetics/metabolism
MH  - Mice
MH  - Mice, Nude
PMC - PMC7374972
OTO - NOTNLM
OT  - Differentiation
OT  - Human induced pluripotent stem cells (hiPSCs)
OT  - Mesoderm
OT  - N7-methylguanosine (m7G)
OT  - Pluripotency
OT  - Vasculogenesis
COIS- The authors declare that they have no competing interests
EDAT- 2020/07/24 06:00
MHDA- 2021/06/22 06:00
PMCR- 2020/07/22
CRDT- 2020/07/24 06:00
PHST- 2020/03/04 00:00 [received]
PHST- 2020/07/06 00:00 [accepted]
PHST- 2020/07/01 00:00 [revised]
PHST- 2020/07/24 06:00 [entrez]
PHST- 2020/07/24 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/07/22 00:00 [pmc-release]
AID - 10.1186/s13287-020-01814-4 [pii]
AID - 1814 [pii]
AID - 10.1186/s13287-020-01814-4 [doi]
PST - epublish
SO  - Stem Cell Res Ther. 2020 Jul 22;11(1):306. doi: 10.1186/s13287-020-01814-4.