Characteristics of quiescent adult neural stem cells induced by the bFGF/BMP4 combination or BMP4 alone in vitro

Sutong Xu; Xi Zhang; Zhuoqun Li; Chenming Liu; Qiulu Liu; Huazhen Chai; Hongkai Yao; Yuping Luo; Siguang Li; Chun Li

doi:10.3389/fncel.2024.1391556

Characteristics of quiescent adult neural stem cells induced by the bFGF/BMP4 combination or BMP4 alone in vitro

Front Cell Neurosci. 2024 May 22:18:1391556. doi: 10.3389/fncel.2024.1391556. eCollection 2024.

Authors

Sutong Xu¹, Xi Zhang², Zhuoqun Li¹, Chenming Liu¹, Qiulu Liu¹, Huazhen Chai¹, Hongkai Yao¹, Yuping Luo^{1

3}, Siguang Li^{1

3}, Chun Li^{1

4}

Affiliations

¹ Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
² Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China.
³ Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopedic Department of Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
⁴ Tongji University Cancer Center, Shanghai Tenth People's Hospital of Tongji University, School of Medicine, Tongji University, Shanghai, China.

Abstract

Bone morphogenetic protein-4 (BMP4) is involved in regulation of neural stem cells (NSCs) proliferation, differentiation, migration and survival. It was previously thought that the treatment of NSCs with BMP4 alone induces astrocytes, whereas the treatment of NSCs with the bFGF/BMP4 combination induces quiescent neural stem cells (qNSCs). In this study, we performed bulk RNA sequencing (RNA-Seq) to compare the transcriptome profiles of BMP4-treated NSCs and bFGF/BMP4-treated NSCs, and found that both NSCs treated by these two methods were Sox2 positive qNSCs which were able to generate neurospheres. However, NSCs treated by those two methods exhibited different characteristics in state and the potential for neuronal differentiation based on transcriptome analysis and experimental results. We found that BMP4-treated NSCs tended to be in a deeper quiescent state than bFGF/BMP4-treated NSCs as the percentage of ki67-positive cells were lower in BMP4-treated NSCs. And after exposure to differentiated environment, bFGF/BMP4-treated NSCs generated more DCX-positive immature neurons and MAP2-positive neurons than BMP4-treated NSCs. Our study characterized qNSCs treated with BMP4 alone and bFGF/BMP4 combination, providing a reference for the scientific use of BMP4 and bFGF/BMP4-induced qNSCs models.

Keywords: BMP4; bFGF/BMP4; differentiation; quiescent neural stem cells; transcriptome.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Authors acknowledge the funding by grants from the National Natural Science Foundation of China (31830111 and 82171387) and Key Research and Innovation Program of Shanghai Municipal Education Commission (2019-01-07-00-07-E00040).