PMID- 27098757
OWN - NLM
STAT- MEDLINE
DCOM- 20171109
LR  - 20210206
IS  - 1573-9546 (Electronic)
IS  - 1573-9538 (Print)
IS  - 1573-9538 (Linking)
VI  - 12
IP  - 3
DP  - 2016 Sep
TI  - Coupling switch of P2Y-IP3 receptors mediates differential Ca(2+) signaling in 
      human embryonic stem cells and derived cardiovascular progenitor cells.
PG  - 465-78
LID - 10.1007/s11302-016-9512-9 [doi]
AB  - Purinergic signaling mediated by P2 receptors (P2Rs) plays important roles in 
      embryonic and stem cell development. However, how it mediates Ca(2+) signals in 
      human embryonic stem cells (hESCs) and derived cardiovascular progenitor cells 
      (CVPCs) remains unclear. Here, we aimed to determine the role of P2Rs in 
      mediating Ca(2+) mobilizations of these cells. hESCs were induced to 
      differentiate into CVPCs by our recently established methods. Gene expression of 
      P2Rs and inositol 1,4,5-trisphosphate receptors (IP3Rs) was analyzed by 
      quantitative/RT-PCR. IP3R3 knockdown (KD) or IP3R2 knockout (KO) hESCs were 
      established by shRNA- or TALEN-mediated gene manipulations, respectively. 
      Confocal imaging revealed that Ca(2+) responses in CVPCs to ATP and UTP were more 
      sensitive and stronger than those in hESCs. Consistently, the gene expression 
      levels of most P2YRs except P2Y1 were increased in CVPCs. Suramin or PPADS 
      blocked ATP-induced Ca(2+) transients in hESCs but only partially inhibited those 
      in CVPCs. Moreover, the P2Y1 receptor-specific antagonist MRS2279 abolished most 
      ATP-induced Ca(2+) signals in hESCs but not in CVPCs. P2Y1 receptor-specific 
      agonist MRS2365 induced Ca(2+) transients only in hESCs but not in CVPCs. 
      Furthermore, IP3R2KO but not IP3R3KD decreased the proportion of hESCs responding 
      to MRS2365. In contrast, both IP3R2 and IP3R3 contributed to UTP-induced Ca(2+) 
      responses while ATP-induced Ca(2+) responses were more dependent on IP3R2 in the 
      CVPCs. In conclusion, a predominant role of P2Y1 receptors in hESCs and a 
      transition of P2Y-IP3R coupling in derived CVPCs are responsible for the 
      differential Ca(2+) mobilization between these cells.
FAU - Huang, Jijun
AU  - Huang J
AD  - Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai 
      Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao 
      Tong University School of Medicine, Shanghai, 200031, China.
AD  - Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, 310009, 
      China.
FAU - Zhang, Min
AU  - Zhang M
AD  - Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai 
      Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao 
      Tong University School of Medicine, Shanghai, 200031, China.
FAU - Zhang, Peng
AU  - Zhang P
AD  - Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai 
      Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao 
      Tong University School of Medicine, Shanghai, 200031, China.
FAU - Liang, He
AU  - Liang H
AD  - Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai 
      Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao 
      Tong University School of Medicine, Shanghai, 200031, China.
AD  - Translational Medical Center for Stem Cell Therapy, Shanghai East Hospital, 
      Tongji University School of Medicine, Shanghai, 200120, China.
FAU - Ouyang, Kunfu
AU  - Ouyang K
AD  - Drug Discovery Center, Key Laboratory of Chemical Genomics, Peking University 
      Shenzhen Graduate School, Shenzhen, 518055, China.
FAU - Yang, Huang-Tian
AU  - Yang HT
AD  - Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai 
      Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao 
      Tong University School of Medicine, Shanghai, 200031, China. htyang@sibs.ac.cn.
AD  - Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, 310009, 
      China. htyang@sibs.ac.cn.
AD  - Translational Medical Center for Stem Cell Therapy, Shanghai East Hospital, 
      Tongji University School of Medicine, Shanghai, 200120, China. htyang@sibs.ac.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160420
PL  - Netherlands
TA  - Purinergic Signal
JT  - Purinergic signalling
JID - 101250499
RN  - 0 (ITPR1 protein, human)
RN  - 0 (Inositol 1,4,5-Trisphosphate Receptors)
RN  - 0 (Receptors, Purinergic P2Y1)
SB  - IM
MH  - Blotting, Western
MH  - Calcium Signaling/*physiology
MH  - Cardiovascular System/*cytology
MH  - Cell Differentiation/physiology
MH  - Flow Cytometry
MH  - Gene Knockdown Techniques
MH  - Gene Knockout Techniques
MH  - Human Embryonic Stem Cells/cytology/*metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Inositol 1,4,5-Trisphosphate Receptors/*metabolism
MH  - Microscopy, Confocal
MH  - Polymerase Chain Reaction
MH  - Receptors, Purinergic P2Y1/*metabolism
PMC - PMC5023627
OTO - NOTNLM
OT  - Ca2+ signaling
OT  - IP3 receptors
OT  - Lineage progenitors
OT  - P2Y receptors
OT  - Pluripotent stem cells
COIS- The authors declare that they have no conflicts of interest.
EDAT- 2016/04/22 06:00
MHDA- 2017/11/10 06:00
PMCR- 2016/10/20
CRDT- 2016/04/22 06:00
PHST- 2015/12/29 00:00 [received]
PHST- 2016/04/04 00:00 [accepted]
PHST- 2016/04/22 06:00 [entrez]
PHST- 2016/04/22 06:00 [pubmed]
PHST- 2017/11/10 06:00 [medline]
PHST- 2016/10/20 00:00 [pmc-release]
AID - 10.1007/s11302-016-9512-9 [pii]
AID - 9512 [pii]
AID - 10.1007/s11302-016-9512-9 [doi]
PST - ppublish
SO  - Purinergic Signal. 2016 Sep;12(3):465-78. doi: 10.1007/s11302-016-9512-9. Epub 
      2016 Apr 20.