CHINA

From China:This study reveals the developmental characteristics and regulatory network of conserved and unconserved evolution of primate ganglion eminence

Ganglionic eminence (GE) is a transient structure in embryonic brain development, from which almost all non-in-situ intermediate neurons originate. Ganglion humps can be divided into three subregions: Lateral ganglion uplift (LGE), intermediate ganglion uplift (MGE) and caudal ganglion uplift (CGE), the subregion of interneurons morphology, fate and function are not the same, interneurons and excitatory neurons together, constitute the neural regulation network of the brain, to maintaining the brain’s arousal/inhibition balance play an important role. Dysregulation of the excitatory/inhibitory balance of neurons in the brain leads to a variety of neurodevelopmental disorders, such as autism and schizophrenia. In addition, differences in the development of ganglion eminence between primates and rodents also play an important role in the number of interneurons and differences in brain size and function between species.

Recently, xu Zhiheng and his team at the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences have published a study in Cell Research. Evolutionarily conservative and non-conservative regulatory Networks during Primate interneuron development were published Revealed by single-cell RNA and ATAC sequencing. In this study, single-cell RNA-SEQ technique was used to analyze the ganglion humps of human and crab-eating rhesus embryos during development. It was found that there were conused cell types in the ganglion humps of human and crab-eating rhesus embryos during 9-13 weeks of gestation, and in crab-eating rhesus embryos during 7-12 weeks of gestation, which could be divided into four large cell groups: neural precursor cells, MGE, LGE and CGE.

Further analysis of the neuronal stem (precursor) cell taxa reveals for the first time that humans and crab-eating macaques have outer radial glia cells (oRG) in ganglion bulges, similar to the more rodent-specific oRG previously found in primates in the cerebral cortex. ORG is thought to be a key factor in larger brain size in primates, suggesting that the larger size of ganglion eminence in primates is also regulated by oRG. The researchers also sequenced human embryonic ganglion eminence using single-cell ATAC-SEQ technology and constructed a regulatory network for ganglion eminence. Through data analysis, we identified a conserve regulatory network in humans and mice, revealing a human-specific regulatory network related to the development of ganglion eminences. For example, the human-specific gene mir9-1Hg plays an important role in regulating the different fates of MGE and LGE.

In this study, single-cell RNA-SEQ and single-cell ATAC-SEQ were used to characterize the gene expression characteristics of ganglion hump in human and cynomolgus macaques, revealing the diversity of cell types and developmental trajectory of ganglion hump in early embryonic development. The study was the first to identify the presence of oRG in the primate ganglion eminence by cross-species comparisons with mice, and identified a series of genes that were highly expressed in primates. Using the single cell ATAC-SEQ regulation network of human ganglion eminence development, we identified human specific genes and related regulatory mechanisms. This study provides clues and data resources for the study of the molecular mechanism of the regulation of the development of ganglion eminence and related diseases.

The research work was supported by the Ministry of Science and Technology, the National Natural Science Foundation of China and the Chinese Academy of Sciences.

Figure 1. Experimental procedure and cell types of ganglion eminence in primates

Figure 2. Primate ganglion eminence progenitor cell types and oRG expression in human and crab-eating macaque ganglion eminence

Ganglionic eminence (GE) is a transient structure in embryonic brain development, from which almost all non-in-situ intermediate neurons originate. Ganglion humps can be divided into three subregions: Lateral ganglion uplift (LGE), intermediate ganglion uplift (MGE) and caudal ganglion uplift (CGE), the subregion of interneurons morphology, fate and function are not the same, interneurons and excitatory neurons together, constitute the neural regulation network of the brain, to maintaining the brain’s arousal/inhibition balance play an important role. Dysregulation of the excitatory/inhibitory balance of neurons in the brain leads to a variety of neurodevelopmental disorders, such as autism and schizophrenia. In addition, differences in the development of ganglion eminence between primates and rodents also play an important role in the number of interneurons and differences in brain size and function between species.

Recently, xu Zhiheng and his team at the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences have published a study in Cell Research. Evolutionarily conservative and non-conservative regulatory Networks during Primate interneuron development were published Revealed by single-cell RNA and ATAC sequencing. In this study, single-cell RNA-SEQ technique was used to analyze the ganglion humps of human and crab-eating rhesus embryos during development. It was found that there were conused cell types in the ganglion humps of human and crab-eating rhesus embryos during 9-13 weeks of gestation, and in crab-eating rhesus embryos during 7-12 weeks of gestation, which could be divided into four large cell groups: neural precursor cells, MGE, LGE and CGE.

Further analysis of the neuronal stem (precursor) cell taxa reveals for the first time that humans and crab-eating macaques have outer radial glia cells (oRG) in ganglion bulges, similar to the more rodent-specific oRG previously found in primates in the cerebral cortex. ORG is thought to be a key factor in larger brain size in primates, suggesting that the larger size of ganglion eminence in primates is also regulated by oRG. The researchers also sequenced human embryonic ganglion eminence using single-cell ATAC-SEQ technology and constructed a regulatory network for ganglion eminence. Through data analysis, we identified a conserve regulatory network in humans and mice, revealing a human-specific regulatory network related to the development of ganglion eminences. For example, the human-specific gene mir9-1Hg plays an important role in regulating the different fates of MGE and LGE.

In this study, single-cell RNA-SEQ and single-cell ATAC-SEQ were used to characterize the gene expression characteristics of ganglion hump in human and cynomolgus macaques, revealing the diversity of cell types and developmental trajectory of ganglion hump in early embryonic development. The study was the first to identify the presence of oRG in the primate ganglion eminence by cross-species comparisons with mice, and identified a series of genes that were highly expressed in primates. Using the single cell ATAC-SEQ regulation network of human ganglion eminence development, we identified human specific genes and related regulatory mechanisms. This study provides clues and data resources for the study of the molecular mechanism of the regulation of the development of ganglion eminence and related diseases.

The research work was supported by the Ministry of Science and Technology, the National Natural Science Foundation of China and the Chinese Academy of Sciences.

Figure 1. Experimental procedure and cell types of ganglion eminence in primates

Figure 2. Primate ganglion eminence progenitor cell types and oRG expression in human and crab-eating macaque ganglion eminence

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