PMID- 25811991
OWN - NLM
STAT- MEDLINE
DCOM- 20160328
LR  - 20181113
IS  - 1528-3658 (Electronic)
IS  - 1076-1551 (Print)
IS  - 1076-1551 (Linking)
VI  - 21
IP  - 1
DP  - 2015 Mar 23
TI  - Human Parthenogenetic Embryonic Stem Cell-Derived Neural Stem Cells Express HLA-G 
      and Show Unique Resistance to NK Cell-Mediated Killing.
PG  - 185-96
LID - 10.2119/molmed.2014.00188 [doi]
AB  - Parent-of-origin imprints have been implicated in the regulation of neural 
      differentiation and brain development. Previously we have shown that, despite the 
      lack of a paternal genome, human parthenogenetic (PG) embryonic stem cells 
      (hESCs) can form proliferating neural stem cells (NSCs) that are capable of 
      differentiation into physiologically functional neurons while maintaining 
      allele-specific expression of imprinted genes. Since biparental ("normal") 
      hESC-derived NSCs (N NSCs) are targeted by immune cells, we characterized the 
      immunogenicity of PG NSCs. Flow cytometry and immunocytochemistry revealed that 
      both N NSCs and PG NSCs exhibited surface expression of human leukocyte antigen 
      (HLA) class I but not HLA-DR molecules. Functional analyses using an in vitro 
      mixed lymphocyte reaction assay resulted in less proliferation of peripheral 
      blood mononuclear cells (PBMC) with PG compared with N NSCs. In addition, natural 
      killer (NK) cells cytolyzed PG less than N NSCs. At a molecular level, expression 
      analyses of immune regulatory factors revealed higher HLA-G levels in PG compared 
      with N NSCs. In line with this finding, MIR152, which represses HLA-G expression, 
      is less transcribed in PG compared with N cells. Blockage of HLA-G receptors ILT2 
      and KIR2DL4 on natural killer cell leukemia (NKL) cells increased cytolysis of PG 
      NSCs. Together this indicates that PG NSCs have unique immunological properties 
      due to elevated HLA-G expression.
FAU - Schmitt, Jessica
AU  - Schmitt J
AD  - Institute for Medical Radiology and Cell Research (MSZ) in the Center for 
      Experimental Molecular Medicine (ZEMM), University of Wurzburg, Wurzburg, 
      Germany.
FAU - Eckardt, Sigrid
AU  - Eckardt S
AD  - Center for Molecular and Human Genetics, The Research Institute at Nationwide 
      Children's Hospital, Columbus, Ohio, United States of America.
FAU - Schlegel, Paul G
AU  - Schlegel PG
AD  - University Children's Hospital Wurzburg, Pediatric Hematology/Oncology, Wurzburg, 
      Germany.
FAU - Siren, Anna-Leena
AU  - Siren AL
AD  - Department of Neurosurgery, Section for Experimental Tumor Immunology, University 
      of Wurzburg, Wurzburg, Germany.
FAU - Bruttel, Valentin S
AU  - Bruttel VS
AD  - University of Wurzburg Medical School, Department of Obstetrics and Gynecology, 
      Section for Experimental Tumor Immunology, University of Wurzburg, Wurzburg, 
      Germany.
FAU - McLaughlin, K John
AU  - McLaughlin KJ
AD  - Center for Molecular and Human Genetics, The Research Institute at Nationwide 
      Children's Hospital, Columbus, Ohio, United States of America.
FAU - Wischhusen, Jorg
AU  - Wischhusen J
AD  - University of Wurzburg Medical School, Department of Obstetrics and Gynecology, 
      Section for Experimental Tumor Immunology, University of Wurzburg, Wurzburg, 
      Germany.
FAU - Muller, Albrecht M
AU  - Muller AM
AD  - Institute for Medical Radiology and Cell Research (MSZ) in the Center for 
      Experimental Molecular Medicine (ZEMM), University of Wurzburg, Wurzburg, 
      Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150323
PL  - England
TA  - Mol Med
JT  - Molecular medicine (Cambridge, Mass.)
JID - 9501023
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-G Antigens)
RN  - 0 (MIRN152 microRNA, human)
RN  - 0 (MicroRNAs)
SB  - IM
MH  - Apoptosis/genetics/immunology
MH  - *Cell Differentiation
MH  - Cell Line
MH  - *Cytotoxicity, Immunologic
MH  - Embryonic Stem Cells/*cytology
MH  - *Gene Expression
MH  - Gene Expression Regulation
MH  - HLA-DR Antigens/genetics/immunology/metabolism
MH  - HLA-G Antigens/*genetics/immunology/metabolism
MH  - Humans
MH  - Killer Cells, Natural/*immunology/metabolism
MH  - MicroRNAs/genetics
MH  - Neural Stem Cells/cytology/*immunology/*metabolism
PMC - PMC4503648
EDAT- 2015/03/27 06:00
MHDA- 2016/03/29 06:00
PMCR- 2015/03/23
CRDT- 2015/03/27 06:00
PHST- 2014/09/20 00:00 [received]
PHST- 2015/03/23 00:00 [accepted]
PHST- 2015/03/27 06:00 [entrez]
PHST- 2015/03/27 06:00 [pubmed]
PHST- 2016/03/29 06:00 [medline]
PHST- 2015/03/23 00:00 [pmc-release]
AID - molmed.2014.00188 [pii]
AID - 14_188_schmitt [pii]
AID - 10.2119/molmed.2014.00188 [doi]
PST - epublish
SO  - Mol Med. 2015 Mar 23;21(1):185-96. doi: 10.2119/molmed.2014.00188.