PMID- 22987393
OWN - NLM
STAT- MEDLINE
DCOM- 20130906
LR  - 20141120
IS  - 1549-4918 (Electronic)
IS  - 1066-5099 (Linking)
VI  - 30
IP  - 12
DP  - 2012 Dec
TI  - Reprogramming of the MHC-I and its regulation by NFkappaB in human-induced 
      pluripotent stem cells.
PG  - 2700-8
LID - 10.1002/stem.1242 [doi]
AB  - The immunogenicity of human pluripotent stem cells plays a major role in their 
      potential use in the clinic. We show that, during their reprogramming, 
      human-induced pluripotent stem (iPS) cells downregulate expression of human 
      leukocyte antigen (HLA)-A/B/C and beta2 microglobulin (beta2M), the two components of 
      major histocompatibility complex-I (MHC-I). MHC-I expression in iPS cells can be 
      restored by differentiation or treatment with interferon-gamma (IFNgamma). To analyze 
      the molecular mechanisms that regulate the expression of the MHC-I molecules in 
      human iPS cells, we searched for correlation between the expression of HLA-A/B/C 
      and beta2M and the expression of transcription factors that bind to the promoter of 
      these genes. Our results show a significant positive correlation between MHC-I 
      expression and expression of the nuclear factors, nuclear factor kappa B 1 
      (NFkappaB1) and RelA, at the levels of RNA, protein and was confirmed by chromatin 
      binding. Concordantly, we detected robust levels of NFkappaB1 and RelA proteins in 
      the nucleus of somatic cells but not in the iPS cell derived from them. 
      Overexpression of NFkappaB1 and RelA in undifferentiated pluripotent stem cells led 
      to induction in expression of MHC-I, whereas silencing NFkappaB1 and RelA by small 
      hairpin RNA decreased the expression of beta2M after IFNgamma treatment. Our data point 
      to the critical role of NFkappaB proteins in regulating the MHC-I expression in human 
      pluripotent stem cells.
CI  - Copyright (c) 2012 AlphaMed Press.
FAU - Pick, Marjorie
AU  - Pick M
AD  - Stem Cell Unit, Department of Genetics, Institute of Life Sciences, The Hebrew 
      University, Jerusalem, Israel.
FAU - Ronen, Daniel
AU  - Ronen D
FAU - Yanuka, Ofra
AU  - Yanuka O
FAU - Benvenisty, Nissim
AU  - Benvenisty N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Stem Cells
JT  - Stem cells (Dayton, Ohio)
JID - 9304532
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (NF-kappa B)
RN  - 0 (Octamer Transcription Factor-3)
RN  - 0 (POU5F1 protein, human)
RN  - 0 (RELA protein, human)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (beta 2-Microglobulin)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Cell Differentiation/drug effects/immunology/physiology
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Cellular Reprogramming/drug effects/genetics/*immunology
MH  - Down-Regulation
MH  - Fibroblasts/cytology
MH  - Histocompatibility Antigens Class I/biosynthesis/genetics/*immunology
MH  - Humans
MH  - Immunochemistry
MH  - Induced Pluripotent Stem Cells/cytology/*immunology/*physiology
MH  - Interferon-gamma/immunology/pharmacology
MH  - Microarray Analysis
MH  - NF-kappa B/biosynthesis/genetics/*immunology/metabolism
MH  - Octamer Transcription Factor-3/antagonists & inhibitors/immunology/metabolism
MH  - Transcription Factor RelA/biosynthesis/genetics/immunology/metabolism
MH  - beta 2-Microglobulin/biosynthesis/immunology
EDAT- 2012/09/19 06:00
MHDA- 2013/09/07 06:00
CRDT- 2012/09/19 06:00
PHST- 2011/09/06 00:00 [received]
PHST- 2012/08/23 00:00 [accepted]
PHST- 2012/09/19 06:00 [entrez]
PHST- 2012/09/19 06:00 [pubmed]
PHST- 2013/09/07 06:00 [medline]
AID - 10.1002/stem.1242 [doi]
PST - ppublish
SO  - Stem Cells. 2012 Dec;30(12):2700-8. doi: 10.1002/stem.1242.