Mild hypothermia promotes neuronal differentiation of human neural stem cells via RBM3-SOX11 signaling pathway

Published: 21 February 2024| Version 1 | DOI: 10.17632/7527hjwbnv.1
, Zhenghui He, 江畅 , Ping Zheng, Zixuan Ma, Qian Liang, Qiao Zhang, Xiongfei Zhao, Jialin Huang,
, Jiyao Jiang,


Both therapeutic hypothermia and neural stem cells (NSCs) transplantation have shown promise in neuroprotection and neural repair after brain injury. However, the effects of therapeutic hypothermia on neuronal differentiation of NSCs are not elucidated. In this study, we aimed to investigate whether mild hypothermia promoted neuronal differentiation in cultured and transplanted human NSCs (hNSCs). A significant increase in neuronal differentiation rate of hNSCs was found when exposing to 35°C, from 33% to 45% in vitro and from 7% to 15% in vivo, respectively. Additionally, single-cell RNA sequencing identified upregulation of RNA-binding motif protein 3 (RBM3) in neuroblast at 35°C, which stabilized the SRY-box transcription factor 11 (SOX11) mRNA and increased its protein expression, leading to an increase in neuronal differentiation of hNSCs. In conclusion, our study highlights that mild hypothermia at 35°C enhances hNSCs-induced neurogenesis through the novel RBM3-SOX11 signaling pathway, and provides a potential treatment strategy in brain disorders.



Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital


Cell Differentiation, Hypothermia, Neural Stem Cell