Induced Pluripotent Stem Cells Reprogrammed with Three Inhibitors Show Accelerated Differentiation Potentials with High Levels of 2-Cell Stage Marker Expression
Summary: Although pluripotent stem cells can generate various types of differentiated cells, it is unclear why lineage-committed stem/progenitor cells derived from pluripotent stem cells are decelerated and why the differentiation-resistant propensity of embryonic stem cell (ESC)/induced pluripotent...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-02-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671119300013 |
| _version_ | 1828915408506191872 |
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| author | Koji Nishihara Takahiro Shiga Eri Nakamura Tomohiko Akiyama Takashi Sasaki Sadafumi Suzuki Minoru S.H. Ko Norihiro Tada Hideyuki Okano Wado Akamatsu |
| author_facet | Koji Nishihara Takahiro Shiga Eri Nakamura Tomohiko Akiyama Takashi Sasaki Sadafumi Suzuki Minoru S.H. Ko Norihiro Tada Hideyuki Okano Wado Akamatsu |
| author_sort | Koji Nishihara |
| collection | DOAJ |
| description | Summary: Although pluripotent stem cells can generate various types of differentiated cells, it is unclear why lineage-committed stem/progenitor cells derived from pluripotent stem cells are decelerated and why the differentiation-resistant propensity of embryonic stem cell (ESC)/induced pluripotent stem cell (iPSC)-derived cells is predominant compared with the in vivo equivalents derived from embryonic/adult tissues. In this study, we demonstrated that iPSCs reprogrammed and maintained with three chemical inhibitors of the fibroblast growth factor 4-mitogen-activated protein kinase cascade and GSK3β (3i) could be differentiated into all three germ layers more efficiently than the iPSCs reprogrammed without the 3i chemicals, even though they were maintained with 3i chemicals once they were reprogrammed. Although the iPSCs reprogrammed with 3i had increased numbers of Zscan4-positive cells, the Zscan4-positive cells among iPSCs that were reprogrammed without 3i did not have an accelerated differentiation ability. These observations suggest that 3i exposure during the reprogramming period determines the accelerated differentiation/maturation potentials of iPSCs that are stably maintained at the distinct state. : Mouse iPSCs reprogrammed and maintained with three chemical inhibitors of the FGF4-MAPK cascade and GSK3β (3i; PD184352, CHIR99021, and SU5402) could be differentiated into all three germ layers efficiently and contain increased numbers of Zscan4, a 2-cell stage marker, positive cells. Keywords: induced pluripotent stem cells (iPSCs), culture conditions, 3i, differentiation potentials, Zscan4, 2-cell genes |
| first_indexed | 2024-12-13T20:13:12Z |
| format | Article |
| id | doaj.art-40748e62b3d34c28a682ce70c8b24703 |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-13T20:13:12Z |
| publishDate | 2019-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-40748e62b3d34c28a682ce70c8b247032022-12-21T23:32:52ZengElsevierStem Cell Reports2213-67112019-02-01122305318Induced Pluripotent Stem Cells Reprogrammed with Three Inhibitors Show Accelerated Differentiation Potentials with High Levels of 2-Cell Stage Marker ExpressionKoji Nishihara0Takahiro Shiga1Eri Nakamura2Tomohiko Akiyama3Takashi Sasaki4Sadafumi Suzuki5Minoru S.H. Ko6Norihiro Tada7Hideyuki Okano8Wado Akamatsu9Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanCenter for Genomic and Regenerative Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, JapanResearch Institute for Diseases of Old Age, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, JapanDepartment of Systems Medicine, Sakaguchi Laboratory, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanCenter for Supercentenarian Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanDepartment of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanDepartment of Systems Medicine, Sakaguchi Laboratory, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, JapanResearch Institute for Diseases of Old Age, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, JapanDepartment of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; Corresponding authorDepartment of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; Center for Genomic and Regenerative Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan; Corresponding authorSummary: Although pluripotent stem cells can generate various types of differentiated cells, it is unclear why lineage-committed stem/progenitor cells derived from pluripotent stem cells are decelerated and why the differentiation-resistant propensity of embryonic stem cell (ESC)/induced pluripotent stem cell (iPSC)-derived cells is predominant compared with the in vivo equivalents derived from embryonic/adult tissues. In this study, we demonstrated that iPSCs reprogrammed and maintained with three chemical inhibitors of the fibroblast growth factor 4-mitogen-activated protein kinase cascade and GSK3β (3i) could be differentiated into all three germ layers more efficiently than the iPSCs reprogrammed without the 3i chemicals, even though they were maintained with 3i chemicals once they were reprogrammed. Although the iPSCs reprogrammed with 3i had increased numbers of Zscan4-positive cells, the Zscan4-positive cells among iPSCs that were reprogrammed without 3i did not have an accelerated differentiation ability. These observations suggest that 3i exposure during the reprogramming period determines the accelerated differentiation/maturation potentials of iPSCs that are stably maintained at the distinct state. : Mouse iPSCs reprogrammed and maintained with three chemical inhibitors of the FGF4-MAPK cascade and GSK3β (3i; PD184352, CHIR99021, and SU5402) could be differentiated into all three germ layers efficiently and contain increased numbers of Zscan4, a 2-cell stage marker, positive cells. Keywords: induced pluripotent stem cells (iPSCs), culture conditions, 3i, differentiation potentials, Zscan4, 2-cell geneshttp://www.sciencedirect.com/science/article/pii/S2213671119300013 |
| spellingShingle | Koji Nishihara Takahiro Shiga Eri Nakamura Tomohiko Akiyama Takashi Sasaki Sadafumi Suzuki Minoru S.H. Ko Norihiro Tada Hideyuki Okano Wado Akamatsu Induced Pluripotent Stem Cells Reprogrammed with Three Inhibitors Show Accelerated Differentiation Potentials with High Levels of 2-Cell Stage Marker Expression Stem Cell Reports |
| title | Induced Pluripotent Stem Cells Reprogrammed with Three Inhibitors Show Accelerated Differentiation Potentials with High Levels of 2-Cell Stage Marker Expression |
| title_full | Induced Pluripotent Stem Cells Reprogrammed with Three Inhibitors Show Accelerated Differentiation Potentials with High Levels of 2-Cell Stage Marker Expression |
| title_fullStr | Induced Pluripotent Stem Cells Reprogrammed with Three Inhibitors Show Accelerated Differentiation Potentials with High Levels of 2-Cell Stage Marker Expression |
| title_full_unstemmed | Induced Pluripotent Stem Cells Reprogrammed with Three Inhibitors Show Accelerated Differentiation Potentials with High Levels of 2-Cell Stage Marker Expression |
| title_short | Induced Pluripotent Stem Cells Reprogrammed with Three Inhibitors Show Accelerated Differentiation Potentials with High Levels of 2-Cell Stage Marker Expression |
| title_sort | induced pluripotent stem cells reprogrammed with three inhibitors show accelerated differentiation potentials with high levels of 2 cell stage marker expression |
| url | http://www.sciencedirect.com/science/article/pii/S2213671119300013 |
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