Establishment of leukemia inhibitory factor (LIF)-independent iPS cells with potentiated Oct4
| Autor: | Meri T. Firpo, Hiroyuki Hirai, Nobuaki Kikyo |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Pluripotency
endocrine system Somatic cell Cellular differentiation Mice Transgenic Biology Transfection Article Kruppel-Like Factor 4 Mice 03 medical and health sciences Transactivation 0302 clinical medicine SOX2 Animals Induced pluripotent stem cell lcsh:QH301-705.5 reproductive and urinary physiology miRNA 030304 developmental biology Medicine(all) 0303 health sciences urogenital system Cell Differentiation Cell Biology General Medicine Embryonic stem cell MicroRNAs Induced pluripotent stem cells lcsh:Biology (General) Leukemia inhibitory factor KLF4 embryonic structures Cancer research Octamer Transcription Factor-3 030217 neurology & neurosurgery Signal Transduction Developmental Biology |
| Zdroj: | Stem Cell Research, Vol 15, Iss 3, Pp 469-480 (2015) |
| ISSN: | 1873-5061 |
| Popis: | Leukemia inhibitory factor (LIF) is widely used to establish and maintain naïve 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 90days 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 naïve pluripotency. |
| Databáze: | OpenAIRE |
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