Mild hypothermia promotes neuronal differentiation of human neural stem cells via RBM3-SOX11 signaling pathway
Yuxiao Ma,
Zhenghui He,
Jiangchang Wang,
Ping Zheng,
Zixuan Ma,
Qian Liang,
Qiao Zhang,
Xiongfei Zhao,
Jialin Huang,
Weiji Weng,
Jiyao Jiang,
Junfeng Feng
Affiliations
Yuxiao Ma
Brain Injury Center, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; Shanghai Institute of Head Trauma, Shanghai 200127, China
Zhenghui He
Brain Injury Center, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; Shanghai Institute of Head Trauma, Shanghai 200127, China
Jiangchang Wang
Brain Injury Center, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; Shanghai Institute of Head Trauma, Shanghai 200127, China
Ping Zheng
Department of Neurosurgery, Shanghai Pudong New Area People’s Hospital, Shanghai 201299, China
Zixuan Ma
Brain Injury Center, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; Shanghai Institute of Head Trauma, Shanghai 200127, China
Qian Liang
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Qiao Zhang
Brain Injury Center, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; Shanghai Institute of Head Trauma, Shanghai 200127, China
Xiongfei Zhao
Shanghai Angecon Biotechnology Co., Ltd., Shanghai 201318, China
Jialin Huang
Brain Injury Center, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; Shanghai Institute of Head Trauma, Shanghai 200127, China
Weiji Weng
Brain Injury Center, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; Shanghai Institute of Head Trauma, Shanghai 200127, China; Corresponding author
Jiyao Jiang
Brain Injury Center, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; Shanghai Institute of Head Trauma, Shanghai 200127, China; Corresponding author
Junfeng Feng
Brain Injury Center, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; Shanghai Institute of Head Trauma, Shanghai 200127, China; Corresponding author
Summary: 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 exposed to 35°C, from 33% to 45% in vitro and from 7% to 15% in vivo. 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.
