Decoding the development of the human hippocampus

Zhong, Shaobo; Ding, Wenbing; Sun, Le; Lü, Yongtao; Dong, Hao; Fan, Xiaoying; Liu, Zeyuan; Chen, Ruiguo; Zhang, Shu; Ma, Qiang; Tang, Fuchou; Wu, Qian; Wang, Xiaoqun

doi:10.1038/s41586-019-1917-5

Cited by 146 publications

(131 citation statements)

References 41 publications

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“…Interestingly, a recent single-cell transcriptomic study of the developing human hippocampus found that microglia were divided into 11 sub-clusters (Zhong et al, 2020), demonstrating that hippocampal microglia are not uniform during human development.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Complement C3-dependent glutamatergic synapse elimination in the developing hippocampus is region- and synapse-specific

Salter

Liu

Choi

et al. 2020

Preprint

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The complement cascade is an innate immune pathway that, in addition to host defense against pathogens, actively maintains tissue homeostasis. Complement is necessary for synaptic pruning during development and drives aberrant synapse loss in a number of neurodegenerative disorders that affect the hippocampus. However, the physiological function of complement in hippocampal synapse development is unknown. To address this, we investigated C3 -/mice at P16-18. We found that VGLUT2 + synapses were increased in the CA1 stratum lacunosum moleculare (SLM) and dentate gyrus molecular layer (DGML) of C3 -/mice compared to wildtype. Conversely, VGLUT1 + synapses, inhibitory synapses and myelin were not affected in the CA1 stratum radiatum (SR), SLM or DGML of C3 -/mice. Finally, we found that there was a decrease in microglial phagocytic activity only in VGLUT2 + regions and this correlated with the amount of VGLUT2 + synapses. Our study elucidates a role of the complement cascade in regulating hippocampus synapse number with exceptional specificity for VGLUT2-containing synapses during development.

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Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Complement C3-dependent glutamatergic synapse elimination in the developing hippocampus is region- and synapse-specific

Salter

Liu

Choi

et al. 2020

Preprint

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“…Multi-omics integration of single-cell transcriptome and ATAC-seq in organ development can provide a robust foundation for the clinical treatment of diseases. For example, by revealing the critical time points and gene regulatory networks of human hippocampus development from a comprehensive perspective, researchers provided information on potential cell groups involved in the pathology of Parkinson's disease, Alzheimer's disease and Huntington's disease [74].…”

Section: Single-cell Approaches To Probe Developmental Processes In Omentioning

confidence: 99%

Profiling chromatin regulatory landscape: insights into the development of ChIP-seq and ATAC-seq

Zhang

2020

Mol Biomed

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Chromatin regulatory landscape plays a critical role in many disease processes and embryo development. Epigenome sequencing technologies such as chromatin immunoprecipitation sequencing (ChIP-seq) and assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) have enabled us to dissect the pan-genomic regulatory landscape of cells and tissues in both time and space dimensions by detecting specific chromatin state and its corresponding transcription factors. Pioneered by the advancement of chromatin immunoprecipitation-chip (ChIP-chip) technology, abundant epigenome profiling technologies have become available such as ChIP-seq, DNase I hypersensitive site sequencing (DNase-seq), ATAC-seq and so on. The advent of single-cell sequencing has revolutionized the next-generation sequencing, applications in single-cell epigenetics are enriched rapidly. Epigenome sequencing technologies have evolved from low-throughput to high-throughput and from bulk sample to the single-cell scope, which unprecedentedly benefits scientists to interpret life from different angles. In this review, after briefly introducing the background knowledge of epigenome biology, we discuss the development of epigenome sequencing technologies, especially ChIP-seq & ATAC-seq and their current applications in scientific research. Finally, we provide insights into future applications and challenges.

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“…Mouse astrocytes reach maturity roughly around one month of age as determined by morphology and gene expression (Bushong et al, 2004;Zhang et al, 2014Zhang et al, , 2016. A single cell RNA-seq study of human and mouse brains found that molecular features of gestational week 16-20 human brains are similar to postnatal day 0-5 (P0-P5) mouse brains (Zhong et al, 2020).…”

Section: Immunopanning Purification Of Astrocytesmentioning

confidence: 99%

Conservation and divergence of vulnerability and responses to stressors between human and mouse astrocytes

Pan

Godoy

et al. 2020

Preprint

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Human-mouse differences are a major barrier in translational research.Astrocytes play important roles in neurological disorders such as stroke, injury, and neurodegeneration. However, the similarities and differences between human and mouse astrocytes are largely unknown. Combining analyses of acutely purified astrocytes, experiments using serum-free cultures of primary astrocytes, and xenografted chimeric mice, we found extensive conservation in astrocytic gene expression between human and mouse. However, genes involved in defense response and metabolism showed species differences. Human astrocytes exhibited greater susceptibility to oxidative stress than mouse astrocytes, due to differences in mitochondria physiology and detoxification pathways. Mouse astrocytes, but not human astrocytes, activate a molecular program for neural repair under hypoxia. Human astrocytes, but not mouse astrocytes, activate the antigen presentation pathway under inflammatory conditions. These species-dependent properties of astrocytes may contribute to differences between mouse models and human neurological and psychiatric disorders.

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Decoding the development of the human hippocampus

Cited by 146 publications

References 41 publications

WITHDRAWN: Complement C3-dependent glutamatergic synapse elimination in the developing hippocampus is region- and synapse-specific

WITHDRAWN: Complement C3-dependent glutamatergic synapse elimination in the developing hippocampus is region- and synapse-specific

Profiling chromatin regulatory landscape: insights into the development of ChIP-seq and ATAC-seq

Conservation and divergence of vulnerability and responses to stressors between human and mouse astrocytes

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