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| Status |
Public on Feb 19, 2024 |
| Title |
Polygenic Risk for Alcohol Use Disorder Affects Cellular Responses to Ethanol Exposure in a Human Microglial Cell Model I |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Polygenic risk scores (PRS) assess genetic susceptibility to Alcohol Use Disorder (AUD), yet their molecular implications remain underexplored. Neuroimmune interactions, particularly in microglia, are recognized as significant contributors to AUD pathophysiology. We investigated the interplay between AUD PRS and ethanol in human microglia derived from iPSCs from individuals with high-or low-PRS (HPRS or LPRS) of AUD. Ethanol exposure induced elevated CD68 expression and morphological changes in microglia, with differential responses between HPRS and LPRS microglial cells. Transcriptomic analysis revealed expression differences in MHCII complex and phagocytosis-related genes following ethanol exposure; HPRS microglial cells displayed enhanced phagocytosis and increased CLEC7Aexpression, unlike LPRS microglial cells. Synapse numbers in co-cultures of induced neurons with microglia after alcohol exposure were lower in HRPS co-cultures, suggesting possible excess synapse pruning. This study provides insights into the intricate relationship between AUD PRS, ethanol, and microglial function, potentially influencing neuronal functions in developing AUD.
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| Overall design |
Cultures of microglial cells, differentiated from multiple iPSC lines prepared from subjects with AUD and high polygenic risk (HPRS) and unaffected with low polygenic risk (LPRS) were treated with 75 mM ethanol or untreated. Total cellular RNA was prepared and compared for effects of ethanol treatment or ethanol interaction with AUD-polygenic risk.
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| Contributor(s) |
Li X, Liu J, Kreimer A, Hart RP, Pang ZP |
| Citation(s) |
39514655 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 AA023797 |
Cellular and genomic mechanisms of the impact of ethanol on human neural model |
RUTGERS BIOMEDICAL AND HEALTH SCIENCES |
Zhiping P. Pang |
| U10 AA008401 |
Collaborative Study on the Genetics of Alcoholism (COGA). |
SUNY DOWNSTATE MEDICAL CENTER |
Bernice Porjesz |
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| Submission date |
Feb 16, 2024 |
| Last update date |
Jan 06, 2025 |
| Contact name |
Ronald P. Hart |
| E-mail(s) |
rhart@rutgers.edu
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| Phone |
848-445-1783
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| Organization name |
Rutgers University
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| Department |
Cell Biology & Neuroscience
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| Street address |
604 Allison Rd Rm B430
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| City |
Piscataway |
| State/province |
NJ |
| ZIP/Postal code |
08854 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (18)
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| GSM8083846 |
Microglia, control, cell line 206 |
| GSM8083847 |
Microglia, control, cell line 399 |
| GSM8083848 |
Microglia, control, cell line 528 |
| GSM8083849 |
Microglia, control, cell line 838 |
| GSM8083850 |
Microglia, control, cell line 864 |
| GSM8083851 |
Microglia, control, cell line 884 |
| GSM8083852 |
Microglia, 75mM ethanol, cell line 92 |
| GSM8083853 |
Microglia, 75mM ethanol, cell line 203 |
| GSM8083854 |
Microglia, 75mM ethanol, cell line 204 |
| GSM8083855 |
Microglia, 75mM ethanol, cell line 206 |
| GSM8083856 |
Microglia, 75mM ethanol, cell line 399 |
| GSM8083857 |
Microglia, 75mM ethanol, cell line 528 |
| GSM8083858 |
Microglia, 75mM ethanol, cell line 838 |
| GSM8083859 |
Microglia, 75mM ethanol, cell line 864 |
| GSM8083860 |
Microglia, 75mM ethanol, cell line 884 |
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| Relations |
| BioProject |
PRJNA1077355 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE255988_MgPRS_raw_counts.tsv.gz |
367.9 Kb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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