PMID- 31358062
OWN - NLM
STAT- MEDLINE
DCOM- 20200625
LR  - 20200625
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 10
IP  - 1
DP  - 2019 Jul 29
TI  - Long noncoding RNA CCDC144NL-AS1 knockdown induces naive-like state conversion of 
      human pluripotent stem cells.
PG  - 220
LID - 10.1186/s13287-019-1323-9 [doi]
LID - 220
AB  - BACKGROUND: Human naive pluripotency state cells can be derived from direct 
      isolation of inner cell mass or primed-to-naive resetting of human embryonic stem 
      cells (hESCs) through different combinations of transcription factors, small 
      molecular inhibitors, and growth factors. Long noncoding RNAs (lncRNAs) have been 
      identified to be crucial in diverse biological processes, including pluripotency 
      regulatory circuit of mouse pluripotent stem cells (PSCs), but few are involved 
      in human PSCs' regulation of pluripotency and naive pluripotency derivation. This 
      study initially planned to discover more lncRNAs possibly playing significant 
      roles in the regulation of human PSCs' pluripotency, but accidently identified a 
      lncRNA whose knockdown in human PSCs induced naive-like pluripotency conversion. 
      METHODS: Candidate lncRNAs tightly correlated with human pluripotency were 
      screened from 55 RNA-seq data containing human ESC, human induced pluripotent 
      stem cell (iPSC), and somatic tissue samples. Then loss-of-function experiments 
      in human PSCs were performed to investigate the function of these candidate 
      lncRNAs. The naive-like pluripotency conversion caused by CCDC144NL-AS1 knockdown 
      (KD) was characterized by quantitative real-time PCR, immunofluorescence 
      staining, western blotting, differentiation of hESCs in vitro and in vivo, 
      RNA-seq, and chromatin immunoprecipitation. Finally, the signaling pathways in 
      CCDC144NL-AS1-KD human PSCs were examined through western blotting and analysis 
      of RNA-seq data. RESULTS: The results indicated that knockdown of CCDC144NL-AS1 
      induces naive-like state conversion of human PSCs in the absence of additional 
      transcription factors or small molecular inhibitors. CCDC144NL-AS1-KD human PSCs 
      reveal naive-like pluripotency features, such as elevated expression of naive 
      pluripotency-associated genes, increased developmental capacity, analogous 
      transcriptional profiles to human naive PSCs, and global reduction of repressive 
      chromatin modification marks. Furthermore, CCDC144NL-AS1-KD human PSCs display 
      inhibition of MAPK (ERK), accumulation of active beta-catenin, and upregulation of 
      some LIF/STAT3 target genes, and all of these are concordant with previously 
      reported traits of human naive PSCs. CONCLUSIONS: Our study unveils an unexpected 
      role of a lncRNA, CCDC144NL-AS1, in the naive-like state conversion of human 
      PSCs, providing a new perspective to further understand the regulation process of 
      human early pluripotency states conversion. It is suggested that CCDC144NL-AS1 
      can be potentially valuable for future research on deriving higher quality naive 
      state human PSCs and promoting their therapeutic applications.
FAU - Wang, Yingying
AU  - Wang Y
AD  - Stem Cell Translational Research Center, Tongji Hospital, Tongji University 
      School of Medicine, Shanghai, 200065, China.
FAU - Guo, Baosen
AU  - Guo B
AD  - College of Life Sciences, Nanchang University, Nanchang, 330031, China.
FAU - Xiao, Zengrong
AU  - Xiao Z
AD  - College of Life Sciences, Nanchang University, Nanchang, 330031, China.
FAU - Lin, Haijun
AU  - Lin H
AD  - College of Life Sciences, Nanchang University, Nanchang, 330031, China.
FAU - Zhang, Xi
AU  - Zhang X
AD  - Stem Cell Translational Research Center, Tongji Hospital, Tongji University 
      School of Medicine, Shanghai, 200065, China.
FAU - Song, Yueqiang
AU  - Song Y
AD  - Stem Cell Translational Research Center, Tongji Hospital, Tongji University 
      School of Medicine, Shanghai, 200065, China.
FAU - Li, Yalei
AU  - Li Y
AD  - College of Life Sciences, Nanchang University, Nanchang, 330031, China.
FAU - Gao, Xuehu
AU  - Gao X
AD  - College of Life Sciences, Nanchang University, Nanchang, 330031, China.
FAU - Yu, Jinjun
AU  - Yu J
AD  - College of Life Sciences, Nanchang University, Nanchang, 330031, China.
FAU - Shao, Zhihua
AU  - Shao Z
AD  - Stem Cell Translational Research Center, Tongji Hospital, Tongji University 
      School of Medicine, Shanghai, 200065, China.
FAU - Li, Xuekun
AU  - Li X
AD  - The Children's Hospital, School of Medicine, Zhejiang University, Hangzhou, 
      310052, China.
FAU - Luo, Yuping
AU  - Luo Y
AD  - Stem Cell Translational Research Center, Tongji Hospital, Tongji University 
      School of Medicine, Shanghai, 200065, China. luoyuping@163.com.
AD  - Human Aging Research Institute and School of Life Science, Nanchang University, 
      Nanchang, 330031, China. luoyuping@163.com.
FAU - Li, Siguang
AU  - Li S
AUID- ORCID: 0000-0002-1740-2060
AD  - Stem Cell Translational Research Center, Tongji Hospital, Tongji University 
      School of Medicine, Shanghai, 200065, China. siguangli@163.com.
AD  - Collaborative Innovation Center for Brain Science, Tongji University, Shanghai, 
      200092, China. siguangli@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190729
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Cell Line
MH  - Cluster Analysis
MH  - Down-Regulation
MH  - Extracellular Signal-Regulated MAP Kinases/genetics/metabolism
MH  - Human Embryonic Stem Cells/cytology/metabolism
MH  - Humans
MH  - Karyotype
MH  - Pluripotent Stem Cells/cytology/metabolism
MH  - RNA Interference
MH  - RNA, Long Noncoding/antagonists & inhibitors/genetics/*metabolism
MH  - RNA, Small Interfering/metabolism
MH  - STAT3 Transcription Factor/genetics/metabolism
MH  - Signal Transduction
MH  - Transcription Factors/genetics/metabolism
MH  - Transcriptome
PMC - PMC6664583
OTO - NOTNLM
OT  - Human PSCs
OT  - Human naive pluripotency
OT  - MAPK/ERK signaling pathway
OT  - Wnt signaling pathway
OT  - lncRNA
COIS- The authors declare that they have no competing interests.
EDAT- 2019/07/31 06:00
MHDA- 2020/06/26 06:00
PMCR- 2019/07/29
CRDT- 2019/07/31 06:00
PHST- 2019/02/17 00:00 [received]
PHST- 2019/07/02 00:00 [accepted]
PHST- 2019/06/18 00:00 [revised]
PHST- 2019/07/31 06:00 [entrez]
PHST- 2019/07/31 06:00 [pubmed]
PHST- 2020/06/26 06:00 [medline]
PHST- 2019/07/29 00:00 [pmc-release]
AID - 10.1186/s13287-019-1323-9 [pii]
AID - 1323 [pii]
AID - 10.1186/s13287-019-1323-9 [doi]
PST - epublish
SO  - Stem Cell Res Ther. 2019 Jul 29;10(1):220. doi: 10.1186/s13287-019-1323-9.