Reprogramming of the MHC-I and its regulation by NFκB in human-induced pluripotent stem cells

Marjorie Pick, Daniel Ronen, Ofra Yanuka, Nissim Benvenisty

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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 β2 microglobulin (β2M), the two components of major histocompatibility complex-I (MHC-I). MHC-I expression in iPS cells can be restored by differentiation or treatment with interferongamma (IFNγ). 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 β2M 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 (NFκB1) and RelA, at the levels of RNA, protein and was confirmed by chromatin binding. Concordantly, we detected robust levels of NFκB1 and RelA proteins in the nucleus of somatic cells but not in the iPS cell derived from them. Overexpression of NFκB1 and RelA in undifferentiated pluripotent stem cells led to induction in expression of MHC-I, whereas silencing NFκB1 and RelA by small hairpin RNA decreased the expression of β2M after IFNγ treatment. Our data point to the critical role of NFκB proteins in regulating the MHC-I expression in human pluripotent stem cells.

Original languageEnglish
Pages (from-to)2700-2708
Number of pages9
JournalStem Cells
Volume30
Issue number12
DOIs
StatePublished - 1 Dec 2012
Externally publishedYes

Keywords

  • Immunogenicity
  • Induced pluripotent stem cells
  • Pluripotent stem cells
  • Reprogramming

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Reprogramming of the MHC-I and its regulation by NFκB in human-induced pluripotent stem cells'. Together they form a unique fingerprint.

Cite this