Introduction
We provide a detailed multi-omics view on the spatial and temporal changes of different astrocyte populations in response to a high-fat high-sugar diet. Using a combination of proteomics, RNAseq and scRNAseq data and their integrated analysis, together with in vivo labeling of astrocyte specific molecular markers, we show that the anatomical location of astrocytes determines the cellular response to exposure to a high caloric diet. Specifically, our results identify a high sensitivity and strong molecular response of astrocytes located in the arcuate nucleus of the hypothalamus upon exposure to a hypercaloric diet.
Summary of main findings
- Long-term exposure to hypercaloric diet differently affects the transcriptional pattern of astrocytes located in cortex, hippocampus, and hypothalamus, with the most prominent changes in the proteomic profile of hypothalamic astrocytes.
- Unlike other cell types in the ARC, astrocytes rapidly respond to hypercaloric diet with a remarkable, yet transient, transcriptional activation.
- The number of astrocytes expressing the astrocytic markers Aldh1L1 and GFAP increases upon a high-fat high-sugar (HFHS) diet feeding in a intraregional- and time- dependent manner.
- The spatial location of Aldh1L1- and GFAP- expressing astrocytes in the ARC undergoes a dynamic reorganization in response to hypercaloric diet.
Overview
Given that the CNS control of metabolism highly depends on functional hypothalamic astrocyteneuron interactions we find our insights into the rapid and selective changes in astrocytes in response to a hypercaloric diet, prior to significant changes in body weight, inflammation, and insulin sensitivity, of particular interest. We provide a comprehensive multi-omics data collection on astrocytes and other cell types during different time points of the initial adaptation to a high caloric diet to better understand the cellular circuitries acting in the ARC and their rearrangements in response to HFHS diet. Of note, our spatial point pattern analysis method in itself provides an advancement to cell analysis in various disciplines and experimental setups, helping to describe the anatomy at a cellular level.
Data and analysis
All the data required for performing the analysis and publisch in the reference articles will be soon deposited in the National Center for Biotechnology Information Gene Expression Omnibus (GEO) and are accessible through the GEO Series accession numbers:
| Data type | Link to the data | Notebook |
|---|---|---|
| Transcriptomics | GSE205313 |
transcriptomics_analysis_v1.ipynb |
| Proteomics | ProtData |
proteomics_analysis_v1.ipynb |
| Singel-Cell RNA-Seq | GSE205667 |
astrocyte_scRNAseq_cluster_approach.ipynb |
| Astrocyte spatial point patterns | ASPP_data |
Csppa_analysis.ipynb |
In order to access one of the data set for instance GSE78279 you need to run the code bellow. Unpacking the data requires tar and gunzip, which should already be available on most systems.
cd ../ #To get to the main github repo folder
mkdir -p data/AstrocytesHeterogenityARC/
cd data/AstrocytesHeterogenityARC/
wget ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE78nnn/GSE78279/suppl/GSE78279_RAW.tar
mkdir GSE78279_RAW
tar -C GSE78279_RAW -xvf GSE78279_RAW.tar
gunzip GSE78279_RAW/*_Regional_*
License
AstrocytesHeterogenityARC is distributed under the MIT license. Please read the license before using AstrocytesHeterogenityARC, which it is distributed in the LICENSE file.
References
Publications related to AstrocytesHeterogenityARC include:
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Lutomska, L.M., Miok, V., Krahmer, N., González García, I., Gruber, T., Le Thuc, O., De Bernardis Murat, C., Legutko, B., Sterr, M., Saher, G., Lickert, H., Ussar, S., Tschöp, M., Lutter, D., García-Cáceres, C. (2022), Diet triggers specific responses of hypothalamic astrocytes in time and region dependent manner, Glia 70 (10), 1795-2008.
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Lutomska, L.M., Miok, V., Krahmer, N., González García, I., Gruber, T., Le Thuc, O., De Bernardis Murat, C., Legutko, B., Sterr, M., Saher, G., Lickert, H., Ussar, S., Tschöp, M., Lutter, D., García-Cáceres, C.(2021), Hypercaloric diet selectively triggers a transient molecular rearrangement of astrocytes in the arcuate nucleus, bioRxiv, 4(1).
Please cite the publication if you use AstrocytesHeterogenityARC.