Psychiatric risk gene transcription factor 4 preferentially regulates cortical interneuron neurogenesis during early brain development

Yuanyuan Wang; Liya Liu; Mingyan Lin

doi:10.7555/JBR.36.20220074

Volume 36 Issue 4

Jul. 2022

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Yuanyuan Wang, Liya Liu, Mingyan Lin. Psychiatric risk gene transcription factor 4 preferentially regulates cortical interneuron neurogenesis during early brain development[J]. The Journal of Biomedical Research, 2022, 36(4): 242-254. doi: 10.7555/JBR.36.20220074

Citation:

Yuanyuan Wang, Liya Liu, Mingyan Lin. Psychiatric risk gene transcription factor 4 preferentially regulates cortical interneuron neurogenesis during early brain development[J]. The Journal of Biomedical Research, 2022, 36(4): 242-254. doi: 10.7555/JBR.36.20220074

Citation:

Yuanyuan Wang, Liya Liu, Mingyan Lin. Psychiatric risk gene transcription factor 4 preferentially regulates cortical interneuron neurogenesis during early brain development[J]. The Journal of Biomedical Research, 2022, 36(4): 242-254. doi: 10.7555/JBR.36.20220074

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Psychiatric risk gene transcription factor 4 preferentially regulates cortical interneuron neurogenesis during early brain development

doi: 10.7555/JBR.36.20220074

Yuanyuan Wang^{1, △},
Liya Liu^{2, △},
Mingyan Lin^{2
,
,}

1.
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, China
2.
Department of Neurobiology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu 211166, China

More Information

Corresponding author: Mingyan Lin, Department of Neurobiology, School of Basic Medical Sciences, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu 211166, China. Tel: +86-25-86869432, E-mail: linmingyan@njmu.edu.cn
Received: 2022-04-05
Revised: 2022-05-31
Accepted: 2022-06-01

Published: 2022-07-28

Issue Date: 2022-07-28

Abstract

Abstract

Genetic variants within or near the transcription factor 4 gene (TCF4) are robustly implicated in psychiatric disorders including schizophrenia. However, the biological pleiotropy poses considerable obstacles to dissect the potential relationship between TCF4 and those highly heterogeneous diseases. Through integrative transcriptomic analysis, we demonstrated that TCF4 is preferentially expressed in cortical interneurons during early brain development. Therefore, disruptions of interneuron development might be the underlying contribution of TCF4 perturbation to a range of neurodevelopmental disorders. Here, we performed chromatin immunoprecipitation sequencing (ChIP-seq) of TCF4 on human medial ganglionic eminence-like organoids (hMGEOs) to identify genome-wide TCF4 binding sites, followed by integration of multi-omics data from human fetal brain. We observed preferential expression of the isoform TCF4-B over TCF4-A. De novo motif analysis found that the identified 5916 TCF4 binding sites are significantly enriched for the E-box sequence. The predicted TCF4 targets in general have positively correlated expression levels with TCF4 in the cortical interneurons, and are primarily involved in biological processes related to neurogenesis. Interestingly, we found that TCF4 interacts with non-bHLH proteins such as FOS/JUN, which may underlie the functional specificity of TCF4 in hMGEOs. This study highlights the regulatory role of TCF4 in interneuron development and provides compelling evidence to support the biological rationale linking TCF4 to the developing cortical interneuron and psychiatric disorders.
- transcription factor 4,
- hMGEOs,
- cortical interneuron,
- ChIP-seq,
- neurogenesis,
- schizophrenia

CLC number: R749.4, Document code: A
The authors reported no conflict of interests.
ρ These authors contributed equally to this work.

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References(39)

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