RRC ID 47717
著者 Ikeda M, Toyoshima F.
タイトル Dormant Pluripotent Cells Emerge during Neural Differentiation of Embryonic Stem Cells in a FoxO3-Dependent Manner.
ジャーナル Mol Cell Biol
Abstract One major concern over the clinical application of embryonic stem cell (ESC)-derived cells is the potentiation of latent tumorigenicity by residual undifferentiated cells. Despite the use of intensive methodological approaches to eliminate residual undifferentiated cells, the properties of these cells remain elusive. Here, we show that under a serum-free neural differentiation condition, residual undifferentiated cells markedly delay progression of their cell cycle without compromising their pluripotency. This dormant pluripotency was maintained during reculture of the cells under a serum-free condition, whereas upon serum stimulation, the cells exited the dormant state and restarted proliferation and differentiation into all three germ layers. Microarray analysis revealed a set of genes that is significantly upregulated in the dormant ESCs compared with their levels of regulation in proliferating ESCs. Among them, we identified the transcription factor Forkhead box O3 (FoxO3) to be an essential regulator of the maintenance of pluripotency in dormant ESCs. Our study demonstrates that the transition into the dormant state endows residual undifferentiated cells with FoxO3-dependent and leukemia inhibitory factor/serum-independent pluripotency.
巻・号 37(5)
公開日 2017-3-1
DOI 10.1128/MCB.00417-16
PII MCB.00417-16
PMID 27956699
PMC PMC5311243
MeSH Animals Cell Culture Techniques Cell Cycle Checkpoints / drug effects Cell Differentiation* / drug effects Cell Self Renewal / drug effects Cells, Cultured Forkhead Box Protein O3 / metabolism* Mice Mouse Embryonic Stem Cells / cytology* Mouse Embryonic Stem Cells / drug effects Mouse Embryonic Stem Cells / metabolism* Neurons / cytology* Neurons / drug effects Neurons / metabolism Octamer Transcription Factor-3 / metabolism Quinolones / pharmacology Up-Regulation / drug effects Up-Regulation / genetics
IF 3.611
引用数 3
リソース情報
遺伝子材料 CSII-EF-mRFP1-RfA (RDB12128)
ヒト・動物細胞 EB5(AES0151) OLV2-1(AES0153)