Naive-like ESRRB+ iPSCs with the Capacity for Rapid Neural Differentiation

• Published in: Stem cell reports Vol. 9; no. 6; pp. 1825 - 1838
• Main Authors: Kisa, Fumihiko, Shiozawa, Seiji, Oda, Keisuke, Yoshimatsu, Sho, Nakamura, Mari, Koya, Ikuko, Kawai, Kenji, Suzuki, Sadafumi, Okano, Hideyuki
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.12.2017; Elsevier
• Subjects: human iPSC; naive pluripotency; neural differentiation; reprogramming; reprogramming; human iPSC; naive pluripotency; neural differentiation
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2017.10.008

Several groups have reported the existence of a form of pluripotency that resembles that of mouse embryonic stem cells (mESCs), i.e., a naive state, in human pluripotent stem cells; however, the characteristics vary between reports. The nuclear receptor ESRRB is expressed in mESCs and plays a significant role in their self-renewal, but its expression has not been observed in most naive-like human induced pluripotent stem cells (hiPSCs). In this study, we modified several methods for converting hiPSCs into a naive state through the transgenic expression of several reprogramming factors. The resulting cells express the components of the core transcriptional network of mESCs, including ESRRB, at high levels, which suggests the existence of naive-state hiPSCs that are similar to mESCs. We also demonstrate that these cells differentiate more readily into neural cells than do conventional hiPSCs. These features may be beneficial for their use in disease modeling and regenerative medicine. [Display omitted] •Induction methods for human naive pluripotent stem cells were optimized•hiPSCs were reprogrammed to a naive-like state with six transcription factors•The resulting naive-like hiPSCs expressed naive state-related genes, including ESRRB•The naive-like hiPSCs differentiated readily into neural and glial cells Kisa et al. modified several methods for converting human induced pluripotent stem cells (hiPSCs) into a naive state, a form of pluripotency that exists in mouse embryonic stem cells (ESCs). Converted cells express components of the core transcriptional network upregulated in mouse ESCs, including ESRRB. They also show that these cells differentiate more readily into neural cells than do conventional hiPSCs.