title: Mouse primed embryonic stem cells could be maintained and reprogrammed on human amnion epithelial cells.
abstract: Naïve and primed embryonic stem cells (ESCs) represent 2 pluripotent states of mouse embryonic stem cells (mESCs), corresponding to the pre- and postimplantation cells, respectively, in vivo. Primed ESCs are distinct from naïve cells in biological characteristics, genetic features, developing potentials, and antagonistic signal pathway dependences to support undifferentiated growth. In vitro, naïve mESCs are readily converted to primed cells upon transferring to primed pluripotency signaling. ESC-derived epiblast stem cells (ESD-EpiSCs) are stabilized primed cells derived from naïve mESCs in vitro, and cannot be maintained with leukemia inhibitory factor (LIF) signaling with or without mouse embryonic fibroblasts as the feeder layer. Here, we show that the undifferentiated growth of ESD-EpiSCs could be maintained with the basic fibroblast growth factor employing human amnion epithelial cells (hAECs) as the feeder layer. Upon exposure to LIF, ESD-EpiSCs could undergo a reprogramming process on hAECs and be converted to naïve-like cells converted ESCs (cESCs), in which naïve pluripotency markers were activated, and primed markers were suppressed. DNA methylation analysis also validated the epigenetic conversion from primed to naïve-like pluripotent status. The bone morphogenetic protein 4 (BMP4) is an important signaling factor in pluripotency controlling, germ cell development, and neural commitment. It showed that ESD-EpiSCs and cESCs exhibited different features toward BMP4. Our results prove that hAECs are ideal feeder cells for both naïve and primed ESCs. More importantly, the primed ESCs are allowed to be reprogrammed to naïve-like pluripotent cells on hAECs. These findings suggest that under suitable conditions primed ESCs have the potency of converting to naïve-like ESCs.
authors.affiliation: Shanghai Jiaotong University, The International Peace Maternity and Child Health Hospital, Shanghai, People's Republic of China.
authors.forename: Yi-Fei
authors.initials: YF
authors.lastname: Chen
authors.forename: Zhangli
authors.initials: Z
authors.lastname: Dong
authors.forename: Lizheng
authors.initials: L
authors.lastname: Jiang
authors.forename: Dongmei
authors.initials: D
authors.lastname: Lai
authors.forename: Lihe
authors.initials: L
authors.lastname: Guo
mesh_terms: D000650:Amnion / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D061252:Feeder Cells / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005855:Germ Layers / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology; D051379:Mice; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D055415:Bone Morphogenetic Protein 4; D053605:Leukemia Inhibitory Factor; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; C513672:Zfp42 protein, mouse; D014157:Transcription Factors; D016222:Fibroblast Growth Factor 2