Monkey multi-organ cell atlas exposed to estrogen.

Area of Science:

• Endocrinology
• Genomics
• Cell Biology

Background:

• Estrogen significantly influences various bodily functions and organ systems.
• Long-term exposure to high estrogen levels can have complex effects on multiple organs.
• Understanding estrogen's molecular mechanisms in different tissues is crucial for health and disease research.

Purpose of the Study:

• To comprehensively analyze the effects of estrogen on major organs using integrated single-cell multi-omics data.
• To dissect cellular heterogeneity, molecular dynamics, and cell-cell communication pathways influenced by estrogen.
• To identify estrogen-induced risk genes associated with various diseases.

Main Methods:

• Single-cell chromatin accessibility sequencing (scCAS) and RNA sequencing (scRNA-seq) were employed.
• Integrated analysis of multi-omics data to create a cellular map of estrogen's effects.
• Pseudotime trajectory inference and cell-cell communication network analysis were performed.
• Integration with human genome-wide association study (GWAS) data.

Main Results:

• An integrated cell map revealed estrogen's impact on molecular dynamics and cell-type composition across major organs.
• Estrogen was shown to induce neutrophil differentiation in liver tissue, affecting endosome-to-lysosome transport.
• Key estrogen-induced risk genes (e.g., AKT1, CCND1, HSPH1) linked to endometrial, breast, and colorectal cancers, as well as COVID-19 and asthma, were identified.

Conclusions:

• This study provides a detailed molecular understanding of estrogen's impact on major organs.
• The findings highlight estrogen's role in cellular processes and disease pathogenesis.
• The generated resource and identified genes offer insights into estrogen-related diseases and potential therapeutic targets.