title: Status of genomic imprinting in epigenetically distinct pluripotent stem cells.
abstract: Mouse epiblast stem cells (EpiSCs) derived from postimplantation embryos are developmentally and functionally different from embryonic stem cells (ESCs) generated from blastocysts. EpiSCs require Activin A and FGF2 signaling for self-renewal, similar to human ESCs (hESCs), while mouse ESCs require LIF and BMP4. Unlike ESCs, EpiSCs have undergone X-inactivation, similar to the tendency of hESCs. The shared self-renewal and X-inactivation properties of EpiSCs and hESCs suggest that they have an epigenetic state distinct from ESCs. This hypothesis predicts that EpiSCs would have monoallelic expression of most imprinted genes, like that observed in hESCs. Here, we confirm this prediction. By contrast, we find that mouse induced pluripotent stem cells (iPSCs) tend to lose imprinting similar to mouse ESCs. These findings reveal that iPSCs have an epigenetic status associated with their pluripotent state rather than their developmental origin. Our results also reinforce the view that hESCs and EpiSCs are in vitro counterparts, sharing an epigenetic status distinct from ESCs and iPSCs.
authors: The Anne McLaren Laboratory for Regenerative Medicine, Department of Surgery, University of Cambridge, Cambridge, United Kingdom.
authors: Bowen
authors: B
authors: Sun
authors: Mitsuteru
authors: M
authors: Ito
authors: Sasha
authors: S
authors: Mendjan
authors: Yoko
authors: Y
authors: Ito
authors: I Gabrielle M
authors: IG
authors: Brons
authors: Adele
authors: A
authors: Murrell
authors: Ludovic
authors: L
authors: Vallier
authors: Anne C
authors: AC
authors: Ferguson-Smith
authors: Roger A
authors: RA
authors: Pedersen
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000378:metabolism; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting; D005855:Germ Layers / Q000166:cytology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism; D051379:Mice; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; C513672:Zfp42 protein, mouse; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014157:Transcription Factors