Naive-like Conversion Overcomes the Limited Differentiation Capacity of Induced Pluripotent Stem Cells

• Published in: The Journal of biological chemistry Vol. 288; no. 36; pp. 26157 - 26166
• Main Authors: Honda, Arata, Hatori, Masanori, Hirose, Michiko, Honda, Chizumi, Izu, Haruna, Inoue, Kimiko, Hirasawa, Ryutaro, Matoba, Shogo, Togayachi, Sumie, Miyoshi, Hiroyuki, Ogura, Atsuo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06-09-2013; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Astrocytes - cytology; Astrocytes - metabolism; Cell Culture; Cell Differentiation; Cells, Cultured; Developmental Biology; Embryonic Stem Cell; Embryonic Stem Cells - cytology; Embryonic Stem Cells - metabolism; Induced Pluripotent Stem (iPS) Cell; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - metabolism; Naive; Neural Stem Cells - cytology; Neural Stem Cells - metabolism; Neurodifferentiation; Oligodendrocytes; Oligodendroglia - cytology; Oligodendroglia - metabolism; Primed; Rabbit; Rabbits; Neurodifferentiation; Oligodendrocytes; Rabbit; Cell Culture; Induced Pluripotent Stem (iPS) Cell; Embryonic Stem Cell; Naive; Primed
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M113.502492

Although induced pluripotent stem (iPS) cells are indistinguishable from ES cells in their expression of pluripotent markers, their differentiation into targeted cells is often limited. Here, we examined whether the limited capacity of iPS cells to differentiate into neural lineage cells could be mitigated by improving their base-line level of pluripotency, i.e. by converting them into the so-called “naive” state. In this study, we used rabbit iPS and ES cells because of the easy availability of both cell types and their typical primed state characters. Repeated passages of the iPS cells permitted their differentiation into early neural cell types (neural stem cells, neurons, and glial astrocytes) with efficiencies similar to ES cells. However, unlike ES cells, their ability to differentiate later into neural cells (oligodendrocytes) was severely compromised. In contrast, after these iPS cells had been converted to a naive-like state, they readily differentiated into mature oligodendrocytes developing characteristic ramified branches, which could not be attained even with ES cells. These results suggest that the naive-like conversion of iPS cells might endow them with a higher differentiation capacity.
Background: The quality of induced pluripotent stem (iPS) cells might be inherently worse than embryonic stem cells.
Results: Although the differentiation capacity of iPS cells is limited, it can be enhanced.
Conclusion: Improving their level of pluripotency alleviated the limited capacity of iPS cells.
Significance: This report offers an effective strategy for the development of iPS cell-based research.