期刊
STEM CELL RESEARCH
卷 15, 期 3, 页码 469-480出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.scr.2015.09.002
关键词
Induced pluripotent stem cells; Leukemia inhibitory factor; miRNA; Pluripotency
资金
- NIH [P30 CA077598, R01 GM098294, R21 CA187232]
- Richard M. Schulze Family Foundation
- Engdahl Family Foundation
- University of Minnesota [22802]
- University of Minnesota Foundation [4160-9227-13]
Leukemia inhibitory factor (LIF) is widely used to establish and maintain naive pluripotent stem cells, including mouse embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Although the combination of chemical inhibitors called 2i can establish mouse iPSCs without LIF from primed pluripotent stem cells, it has been difficult, if not impossible, to establish mouse iPSCs from differentiated somatic cells without LIF. We previously showed that the fusion gene of the transactivation domain of MyoD and the full-length Oct4 (M3O) increases the efficiency of making iPSCs when transduced into fibroblasts along with Sox2, Klf4, and c-Myc (M3O-SKM). Here, we report that M3O-SKM allows for establishment of iPSCs without exogenous LIF from mouse embryonic fibroblasts. The established iPSCs remained undifferentiated and maintained pluripotency over 90 days without LIF as long as M3O was expressed. The iPSCs upregulated miR-205-5p, which was potentially involved in the LIF-independence by suppressing the two signaling pathways inhibited by 2i. The result indicates that potentiated Oct4 can substitute for the LIF signaling pathway, providing a novel model to link Oct4 and LIF, two of the most significant players in naive pluripotency. (C) 2015 The Authors. Published by Elsevier B.V.
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