Volume 32, No 5, May 2022

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 32 Issue 5, May 2022: 425-436   |  Open Access

ORIGINAL ARTICLES

Evolutionarily conservative and non-conservative regulatory networks during primate interneuron development revealed by single-cell RNA and ATAC sequencing

Ziqi Zhao^1,2,† , Dan Zhang^1,2,† , Fuqiang Yang^1,2,† , Mingrui Xu^1,2 , Shaoli Zhao^1,2 , Taotao Pan³ , Chuanyu Liu^3,4 , Yongjie Liu^1,2,5,6 , Qingfeng Wu^1,2 , Qiang Tu^2,5,6 , Ping Zhou⁷ , Rong Li⁷ , Jia Kang⁸ , Lan Zhu⁸ , Fei Gao^2,9 , Yaqing Wang^1,2,* , Zhiheng Xu^1,2,*

¹State Key Laboratory of Molecular Developmental Biology, CAS Center for Excellence in Brain Science and Intelligence Technology, School of Future Technology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
²University of Chinese Academy of Sciences, Beijing, China
³BGI-Beijing, Beijing, China
⁴BGIShenzhen, Shenzhen, China
⁵State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Innovation Academy for Seed Design, Chinese Academy of Sciences, Beijing, China
⁶Key Laboratory of Genetic Network Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
⁷Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
⁸Department of Obstetrics and Gynecology, Beijing, China
⁹State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
^†These authors contributed equally: Ziqi Zhao, Dan Zhang, Fuqiang Yang
Correspondence: Yaqing Wang(yqwang@genetics.ac.cn)Zhiheng Xu(zhxu@genetics.ac.cn)

The differences in size and function between primate and rodent brains, and the association of disturbed excitatory/inhibitory balance with many neurodevelopmental disorders highlight the importance to study primate ganglionic eminences (GEs) development. Here we used single-cell RNA and ATAC sequencing to characterize the emergence of cell diversity in monkey and human GEs where most striatal and cortical interneurons are generated. We identified regional and temporal diversity among progenitor cells which give rise to a variety of interneurons. These cells are specified within the primate GEs by well conserved gene regulatory networks, similar to those identified in mice. However, we detected, in human, several novel regulatory pathways or factors involved in the specification and migration of interneurons. Importantly, comparison of progenitors between our human and published mouse GE datasets led to the discovery and confirmation of outer radial glial cells in GEs in human cortex. Our findings reveal both evolutionarily conservative and nonconservative regulatory networks in primate GEs, which may contribute to their larger brain sizes and more complex

https://doi.org/10.1038/s41422-022-00635-9

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