NEUROD1 efficiently converts peripheral blood cells into neurons with partial reprogramming by pluripotency factors

• 成果类型: Article
• 署名作者: Saito, Yoichi; Ishikawa, Mitsuru; Ohkuma, Mahito; Moody, Jonathan; Mabuchi, Yo; Sanosaka, Tsukasa; Ando, Yoshinari; Yamashita, Takayuki; Hon, Chung Chau; Shin, Jay W.; Akamatsu, Wado; Okano, Hideyuki
• 署名单位: Keio University; Keio University; Fujita Health University; Fujita Health University; RIKEN; Fujita Health University; Hiroshima University; Agency for Science Technology & Research (A*STAR); A*STAR - Genome Institute of Singapore (GIS); National University of Singapore; Juntendo University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8979
• DOI: 10.1073/pnas.2401387122
• 发表日期: 2025-05-06
• 关键词: stem-cells; human fibroblasts; generation; specification; induction; mouse; myc

摘要

The direct reprogramming of cells has tremendous potential in in vitro neurological studies. Previous attempts to convert blood cells into induced neurons have presented several challenges, necessitating a less invasive, efficient, rapid, and convenient approach. The current study introduces an optimized method for converting somatic cells into neurons using a nonsurgical approach that employs peripheral blood cells as an alternative source to fibroblasts. We have demonstrated the efficacy of a unique combination of transcription factors, including NEUROD1, and four Yamanaka reprogramming factors (OCT3/4, SOX2, KLF4, and c-MYC), in generating glutamatergic neurons within 3 wk. This approach, which requires only five pivotal factors (NEUROD1, OCT3/4, SOX2, KLF4, and c-MYC), has the potential to create functional neurons and circumvents the need for induced pluripotent stem cell (iPSC) intermediates, as evidenced by single-cell RNA sequencing and whole-genome bisulfite sequencing, along with lineage-tracing experiments using Cre-LoxP system. While fibroblasts have been widely used for neuronal reprogramming, our findings suggest that peripheral blood cells offer a potential alternative, particularly in contexts where minimally invasive sampling and procedures convenient for patients are emphasized. This method provides a rapid strategy for modeling neuronal diseases and contributes to advancements in drug discovery and personalized medicine.