DOI: 10.5061/dryad.r7sqv9sq4
title: Brain-derived exosomal hemoglobin transfer contributes to neuronal mitochondrial homeostasis under hypoxia

description: Hypoxia is an important physiological stress that causes nerve injuries
 and several brain diseases. However, the mechanism of brain response to
 hypoxia remains unclear, thus limiting the development of interventional
 strategies. This study conducted combined analyses of single-nucleus
 transcriptome sequencing and extracellular vesicle transcriptome
 sequencing on hypoxic mouse brains, described cell-cell communication in
 the brain under hypoxia from intercellular and extracellular dimensions,
 confirmed that hemoglobin mRNA was transferred from non-neuronal cells to
 neurons, and eventually expressed. Then we further explored the role of
 exosomal hemoglobin transfer in vitro, using human-derived cell lines, and
 clarified that hypoxia promoted the transfer and expression of exosomal
 hemoglobin between endothelial cells and neurons. And we found the vital
 function of exosomal hemoglobin to protect against neurological injury by
 maintaining mitochondrial homeostasis in neurons. In conclusion, this
 study identified a novel mechanism of ‘mutual aid’ in hypoxia responses in
 the brain, involving exosomal hemoglobin transfer, clarified the important
 role of exosomal communication in the process of brain stress response,
 and provided a novel interventional perspective for hypoxia-related brain
 diseases.
description: # Brain-derived exosomal hemoglobin transfer contributes to neuronal
 mitochondrial homeostasis under hypoxia Dataset DOI:
 [10.5061/dryad.r7sqv9sq4](10.5061/dryad.r7sqv9sq4) ## Description of the
 data and file structure This dataset contains processed single-nucleus RNA
 sequencing (snRNA-seq) data obtained from mouse brain tissue under chronic
 hypoxia. Two experimental groups were included: a control group and a
 group exposed to hypoxia for 14 days. The data were generated to
 investigate transcriptional alterations and cell-type-level responses
 associated with prolonged hypoxic stress in the brain. ### Files and
 variables #### File: snRNA\_Con\_H14d\_seurat.rds **Description:**  *
 snRNA_Con_H14d_seurat.rds: An R object in Seurat format containing the
 processed single-nucleus RNA-seq data for two mouse brain experimental
 groups: * "Con": control group * "H14d": mice exposed
 to hypoxia for 28 days #### **Variables contained within the .rds Seurat
 object include:** * **Expression matrix (@assays$RNA@data)** * Normalized
 log-transformed gene expression (log-normalized counts) * Rows: genes;
 Columns: single nuclei * Unit: log-normalized counts * Missing values: not
 applicable (genes with zero counts not explicitly removed) * **Metadata
 (@meta.data)** * orig.ident: Sample group identity (Con or H14d) *
 nFeature_RNA: Number of genes detected per nucleus * nCount_RNA: Total RNA
 counts per nucleus * seurat_clusters: Cluster label assigned by Seurat
 clustering * Other standard Seurat metadata fields ## Code/software This
 dataset is provided as an .rds file containing a Seurat object. To load
 and explore the data, the following free and open-source software is
 required: * **R** (version ≥ 4.1.0) * **Seurat** package (version ≥ 4.3.0)
 Additional packages commonly used in the downstream analysis include: *
 **dplyr**, **ggplot2**, **patchwork** – for data manipulation and
 visualization * **CellChat** (version ≥ 1.6.1) – for intercellular
 communication analysis * **SingleR** (optional) – for reference-based cell
 type annotation ## Access information NA