PMID- 32468734
OWN - NLM
STAT- MEDLINE
DCOM- 20210510
LR  - 20210510
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 24
IP  - 14
DP  - 2020 Jul
TI  - Stage-specific regulation of Gremlin1 on the differentiation and expansion of 
      human urinary induced pluripotent stem cells into endothelial progenitors.
PG  - 8018-8030
LID - 10.1111/jcmm.15433 [doi]
AB  - Human urinary induced pluripotent stem cells (hUiPSCs) produced from exfoliated 
      renal epithelial cells present in urine may provide a non-invasive source of 
      endothelial progenitors for the treatment of ischaemic diseases. However, their 
      differentiation efficiency is unsatisfactory and the underlying mechanism of 
      differentiation is still unknown. Gremlin1 (GREM1) is an important gene involved 
      in cell differentiation. Therefore, we tried to elucidate the roles of GREM1 
      during the differentiation and expansion of endothelial progenitors. HUiPSCs were 
      induced into endothelial progenitors by three stages. After differentiation, 
      GREM1 was obviously increased in hUiPSC-induced endothelial progenitors 
      (hUiPSC-EPs). RNA interference (RNAi) was used to silence GREM1 expression in 
      three stages, respectively. We demonstrated a stage-specific effect of GREM1 in 
      decreasing hUiPSC-EP differentiation in the mesoderm induction stage (Stage 1), 
      while increasing differentiation in the endothelial progenitors' induction stage 
      (Stage 2) and expansion stage (Stage 3). Exogenous addition of GREM1 recombinant 
      protein in the endothelial progenitors' expansion stage (Stage 3) promoted the 
      expansion of hUiPSC-EPs although the activation of VEGFR2/Akt or 
      VEGFR2/p42/44MAPK pathway. Our study provided a new non-invasive source for 
      endothelial progenitors, demonstrated critical roles of GREM1 in hUiPSC-EP and 
      afforded a novel strategy to improve stem cell-based therapy for the ischaemic 
      diseases.
CI  - (c) 2020 The Authors. Journal of Cellular and Molecular Medicine published by 
      Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
FAU - Chen, Haixuan
AU  - Chen H
AD  - Translational Medicine Center, the First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Zhang, Zhen
AU  - Zhang Z
AD  - Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
AD  - Key Laboratory for Stem Cells and Tissue Engineering, Center for Stem Cell 
      Biology and Tissue Engineering, Ministry of Education, Sun Yat-sen University, 
      Guangzhou, China.
FAU - Wang, Zhecun
AU  - Wang Z
AD  - Department of Vascular Surgery, the First Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Li, Quhuan
AU  - Li Q
AD  - Institute of Biomechanics, School of Bioscience and Bioengineering, South China 
      University of Technology, Guangzhou, China.
FAU - Chen, Hui
AU  - Chen H
AD  - Department of Gynecology and Obstetrics, Sun Yat-sen Memorial Hospital, Sun 
      Yat-sen University, Guangzhou, China.
FAU - Guo, Song
AU  - Guo S
AD  - Department of Gynecology and Obstetrics, Sun Yat-sen Memorial Hospital, Sun 
      Yat-sen University, Guangzhou, China.
FAU - Bao, Lin
AU  - Bao L
AD  - Department of Gynecology and Obstetrics, Sun Yat-sen Memorial Hospital, Sun 
      Yat-sen University, Guangzhou, China.
FAU - Wang, Zheng
AU  - Wang Z
AD  - Department of Genetics and Cell Biology, Basic Medical College, Qingdao 
      University, Qingdao, China.
FAU - Min, Wang
AU  - Min W
AUID- ORCID: 0000-0002-2479-6096
AD  - Interdepartmental Program in Vascular Biology and Therapeutics, Department of 
      Pathology, Yale University School of Medicine, New Haven, CT, USA.
FAU - Xiang, Qiuling
AU  - Xiang Q
AUID- ORCID: 0000-0001-9921-8699
AD  - Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
AD  - Key Laboratory for Stem Cells and Tissue Engineering, Center for Stem Cell 
      Biology and Tissue Engineering, Ministry of Education, Sun Yat-sen University, 
      Guangzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200528
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (GREM1 protein, human)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (RNA, Small Interfering)
SB  - IM
MH  - Cell Differentiation/*genetics
MH  - Cell Line
MH  - Endothelial Progenitor Cells/*cytology/*metabolism
MH  - Fluorescent Antibody Technique
MH  - Gene Expression Regulation, Developmental
MH  - Gene Knockdown Techniques
MH  - Gene Silencing
MH  - Humans
MH  - Immunophenotyping
MH  - Induced Pluripotent Stem Cells/*cytology/*metabolism
MH  - Intercellular Signaling Peptides and Proteins/*genetics
MH  - Models, Biological
MH  - RNA, Small Interfering/genetics
PMC - PMC7348142
OTO - NOTNLM
OT  - Gremlin1
OT  - differentiation
OT  - endothelial progenitors
OT  - expansion
OT  - human urinary induced pluripotent stem cells
COIS- All authors declared no conflicts of interest.
EDAT- 2020/05/30 06:00
MHDA- 2021/05/11 06:00
PMCR- 2020/07/01
CRDT- 2020/05/30 06:00
PHST- 2019/12/01 00:00 [received]
PHST- 2020/04/07 00:00 [revised]
PHST- 2020/05/07 00:00 [accepted]
PHST- 2020/05/30 06:00 [pubmed]
PHST- 2021/05/11 06:00 [medline]
PHST- 2020/05/30 06:00 [entrez]
PHST- 2020/07/01 00:00 [pmc-release]
AID - JCMM15433 [pii]
AID - 10.1111/jcmm.15433 [doi]
PST - ppublish
SO  - J Cell Mol Med. 2020 Jul;24(14):8018-8030. doi: 10.1111/jcmm.15433. Epub 2020 May 
      28.