Establishment of leukemia inhibitory factor (LIF)-independent iPS cells with potentiated Oct4
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...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-11-01
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| Series: | Stem Cell Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1873506115001154 |
| _version_ | 1819212854420570112 |
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| author | Hiroyuki Hirai Meri Firpo Nobuaki Kikyo |
| author_facet | Hiroyuki Hirai Meri Firpo Nobuaki Kikyo |
| author_sort | Hiroyuki Hirai |
| collection | DOAJ |
| description | 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 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 naïve pluripotency. |
| first_indexed | 2024-12-23T06:49:35Z |
| format | Article |
| id | doaj.art-a385cf2cc2a54b3f86c894ef67675b80 |
| institution | Directory Open Access Journal |
| issn | 1873-5061 1876-7753 |
| language | English |
| last_indexed | 2024-12-23T06:49:35Z |
| publishDate | 2015-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Research |
| spelling | doaj.art-a385cf2cc2a54b3f86c894ef67675b802022-12-21T17:56:28ZengElsevierStem Cell Research1873-50611876-77532015-11-0115346948010.1016/j.scr.2015.09.002Establishment of leukemia inhibitory factor (LIF)-independent iPS cells with potentiated Oct4Hiroyuki Hirai0Meri Firpo1Nobuaki Kikyo2Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota 55455, USAStem Cell Institute, University of Minnesota, Minneapolis, Minnesota 55455, USAStem Cell Institute, University of Minnesota, Minneapolis, Minnesota 55455, USALeukemia 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 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 naïve pluripotency.http://www.sciencedirect.com/science/article/pii/S1873506115001154Induced pluripotent stem cellsLeukemia inhibitory factormiRNAPluripotency |
| spellingShingle | Hiroyuki Hirai Meri Firpo Nobuaki Kikyo Establishment of leukemia inhibitory factor (LIF)-independent iPS cells with potentiated Oct4 Stem Cell Research Induced pluripotent stem cells Leukemia inhibitory factor miRNA Pluripotency |
| title | Establishment of leukemia inhibitory factor (LIF)-independent iPS cells with potentiated Oct4 |
| title_full | Establishment of leukemia inhibitory factor (LIF)-independent iPS cells with potentiated Oct4 |
| title_fullStr | Establishment of leukemia inhibitory factor (LIF)-independent iPS cells with potentiated Oct4 |
| title_full_unstemmed | Establishment of leukemia inhibitory factor (LIF)-independent iPS cells with potentiated Oct4 |
| title_short | Establishment of leukemia inhibitory factor (LIF)-independent iPS cells with potentiated Oct4 |
| title_sort | establishment of leukemia inhibitory factor lif independent ips cells with potentiated oct4 |
| topic | Induced pluripotent stem cells Leukemia inhibitory factor miRNA Pluripotency |
| url | http://www.sciencedirect.com/science/article/pii/S1873506115001154 |
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