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Decoding brain memory formation by single-cell RNA sequencing.

ABSTRACT: To understand how distinct memories are formed and stored in the brain is an important and fundamental question in neuroscience and computational biology. A population of neurons, termed engram cells, represents the physiological manifestation of a specific memory trace and is characterized by dynamic changes in gene expression, which in turn alters the synaptic connectivity and excitability of these cells. Recent applications of single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq) are promising approaches for delineating the dynamic expression profiles in these subsets of neurons, and thus understanding memory-specific genes, their combinatorial patterns and regulatory networks. The aim of this article is to review and discuss the experimental and computational procedures of sc/snRNA-seq, new studies of molecular mechanisms of memory aided by sc/snRNA-seq in human brain diseases and related mouse models, and computational challenges in understanding the regulatory mechanisms underlying long-term memory formation.

SUBMITTER: Sardoo AM

PROVIDER: S-EPMC9677489 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Decoding brain memory formation by single-cell RNA sequencing.

Sardoo Atlas M AM Zhang Shaoqiang S Ferraro Thomas N TN Keck Thomas M TM Chen Yong Y

Briefings in bioinformatics 20221101 6

To understand how distinct memories are formed and stored in the brain is an important and fundamental question in neuroscience and computational biology. A population of neurons, termed engram cells, represents the physiological manifestation of a specific memory trace and is characterized by dynamic changes in gene expression, which in turn alters the synaptic connectivity and excitability of these cells. Recent applications of single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequ ...[more]

PMID: 36156112

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Project description:BackgroundHip fractures in the elderly have significant consequences, stemming from the initial trauma and subsequent surgeries. Hidden blood loss and stress due to concealed injury sites could impact the whole osteoimmune microenvironment. This study employs scRNA-seq technique to map immune profiles in elderly hip fracture patients from post-trauma to the recovery period, investigating the dynamic changes of immune inflammation regulation subgroups.MethodsWe collected peripheral blood samples from four elderly hip fracture patients (two males and two females, all > 75 years of age) at three different time points (24 h post-trauma, 24 h post-operation, and day 7 post-operation) and applied scRNA-seq technique to analyze the cellular heterogeneity and identify differentially expressed genes in peripheral blood individual immune cells from elderly hip fracture patients.ResultsIn this study, we analyzed the composition and gene expression profiles of peripheral blood mononuclear cells (PBMCs) from elderly hip fracture patients by scRNA-seq and further identified new CD14 monocyte subpopulations based on marker genes and transcriptional profiles. Distinct gene expression changes were observed in various cell subpopulations at different time points. C-Mono2 monocyte mitochondria-related genes were up-regulated and interferon-related and chemokine-related genes were down-regulated within 24 h post-operation. Further analysis of gene expression profiles at day 7 post-operation showed that C-Mono2 monocytes showed downregulation of inflammation-related genes and osteoblast differentiation-related genes. However, the expression of these genes in cytotoxic T cells, Treg cells, and B cell subsets exhibited a contrasting trend. GZMK+CD8+ cytotoxic T cells showed downregulation of chemokine-related genes, and Treg cells showed upregulation of genes related to the JAK/STAT signaling pathway. Furthermore, we examined interactions among diverse immune cell subsets, pinpointing specific ligand-receptor pairs. These findings imply cross-talk and communication between various cell types in the post-traumatic immune response.ConclusionsOur study elucidates the notable alterations in immune cell subpopulations during different stages of hip fracture in elderly patients, both in terms of proportions and differential gene expressions. These changes provide significant clinical implications for tissue repair, infection prevention, and fracture healing in clinic.

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Decoding brain memory formation by single-cell RNA sequencing.

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Decoding brain memory formation by single-cell RNA sequencing.

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