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

摘要: The immunogenicity of human pluripotent stem cells plays a major role in their potential use the clinic. We show that, during reprogramming, human-induced (iPS) downregulate expression leukocyte antigen (HLA)-A/B/C and β2 microglobulin (β2M), two components histocompatibility complex-I (MHC-I). MHC-I iPS can be restored by differentiation or treatment with interferon-gamma (IFNγ). To analyze molecular mechanisms that regulate molecules cells, we searched for correlation between HLA-A/B/C β2M transcription factors bind to promoter these genes. Our results significant positive nuclear factors, factor kappa B 1 (NFκB1) RelA, at levels RNA, protein was confirmed chromatin binding. Concordantly, detected robust NFκB1 RelA proteins nucleus somatic but not cell derived from them. Overexpression undifferentiated led induction MHC-I, whereas silencing small hairpin RNA decreased after IFNγ treatment. data point critical NFκB regulating cells. STEM CELLS 2012;30:2700–2708