Transcriptomic profiling of Dip2a in the neural differentiation of mouse embryonic stem cells

Mingze Yao; Lei Zhang; Xiaojuan Teng; Yu Lei; Xiaoyu Xing; Tinglin Ren; Yuanqing Pan; Liwen Zhang; Zhengfeng Li; Jingxia Lin; Yaowu Zheng; Li Xing; Jiajian Zhou; Changxin Wu

doi:10.1016/j.csbj.2023.12.032

Transcriptomic profiling of Dip2a in the neural differentiation of mouse embryonic stem cells

Comput Struct Biotechnol J. 2023 Dec 27:23:700-710. doi: 10.1016/j.csbj.2023.12.032. eCollection 2024 Dec.

Authors

Mingze Yao¹, Lei Zhang^{1

2}, Xiaojuan Teng³, Yu Lei¹, Xiaoyu Xing¹, Tinglin Ren¹, Yuanqing Pan¹, Liwen Zhang¹, Zhengfeng Li⁴, Jingxia Lin³, Yaowu Zheng¹, Li Xing¹, Jiajian Zhou³, Changxin Wu¹

Affiliations

¹ Institutes of Biomedical Sciences, Shanxi Provincial Key Laboratory for Medical Molecular Cell Biology, Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan 030006, China.
² Center of Reproductive Medicine, Children's Hospital of Shanxi and Women Health Center of Shanxi, Taiyuan 030006, China.
³ Dermatology Hospital, Southern Medical University, Guangzhou 510000, China.
⁴ State Key Laboratory of Respiratory Disease, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510000, China.

Abstract

Introduction: The disconnected-interacting protein 2 homolog A (DIP2A), a member of disconnected-interacting 2 protein family, has been shown to be involved in human nervous system-related mental illness. This protein is highly expressed in the nervous system of mouse. Mutation of mouse DIP2A causes defects in spine morphology and synaptic transmission, autism-like behaviors, and defective social novelty [5], [27], indicating that DIP2A is critical to the maintenance of neural development. However, the role of DIP2A in neural differentiation has yet to be investigated.

Objective: To determine the role of DIP2A in neural differentiation, a neural differentiation model was established using mouse embryonic stem cells (mESCs) and studied by using gene-knockout technology and RNA-sequencing-based transcriptome analysis.

Results: We found that DIP2A is not required for mESCs pluripotency maintenance, but loss of DIP2A causes the neural differentiation abnormalities in both N2B27 and KSR medium. Functional knockout of Dip2a gene also decreased proliferation of mESCs by perturbation of the cell cycle and profoundly inhibited the expression of a large number of neural development-associated genes which mainly enriched in spinal cord development and postsynapse assembly.

Conclusions: The results of this report demonstrate that DIP2A plays an essential role in regulating differentiation of mESCs towards the neural fate.

Keywords: Dip2a; Mouse embryonic stem cell; Neural differentiation; RNA-sequencing.