Histological analyses data for: Multinucleated giant cells are hallmarks of ovarian aging with unique immune and degradation-associated molecular signatures
Data files
Apr 07, 2025 version files 12.82 KB
-
Paper_raw_data.xlsx
11.34 KB
-
README.md
1.47 KB
Abstract
The ovary is one of the first organs to exhibit signs of aging, characterized by reduced tissue function, chronic inflammation, and fibrosis. Multinucleated giant cells (MNGCs), formed by macrophage fusion, typically occur in chronic immune pathologies, including infectious and non-infectious granulomas and the foreign body response, but are also observed in the aging ovary. The function and consequence of ovarian MNGCs remain unknown as their biological activity is highly context-dependent, and their large size has limited their isolation and analysis through technologies such as single-cell RNA sequencing. In this study, we define ovarian MNGCs through a deep analysis of their presence across age and species using advanced imaging technologies as well as their unique transcriptome using laser capture microdissection. MNGCs form complex interconnected networks that increase with age in both mouse and nonhuman primate ovaries. MNGCs are characterized by high Gpnmb expression, a putative marker of ovarian and non-ovarian MNGCs. Pathway analysis highlighted functions in apoptotic cell clearance, lipid metabolism, proteolysis, immune processes, and increased oxidative phosphorylation and antioxidant activity. Thus, MNGCs have signatures related to degradative processes, immune function, and high metabolic activity. These processes were enriched in MNGCs compared to primary ovarian macrophages, suggesting discrete functionality. MNGCs express CD4 and colocalize with T-cells, which were enriched in regions of MNGCs, indicative of a close interaction between these immune cell types. These findings implicate MNGCs in modulation of the ovarian immune landscape during aging given their high penetrance and unique molecular signature that supports degradative and immune functions.
https://doi.org/10.5061/dryad.kh18932j4
Description of the data and file structure
Histological quantification of MNGCs and postitive antibody staining was performed on tissue sections from mouse and non-human primate ovaries using ImageJ. To quantify the amount of ovarian area taken up by MNGCs (figure 1), the Trainable Weka Segmentation plugin in Fiji (NIH) was used to train the model on regions of non-ovary, non-MNGC ovary, and MNGCs. For figure 4, percent positive CD4 or CD3ε area was determined as DAB positive area over the total area of an ROI that included area of MNGCs, corpora lutea, or stroma.
Files and variables
File: Paper_raw_data.xlsx
Description: Raw data from ImageJ analysis of Figures 1C, 1D, 4F, 4G, 4H.
Variables
- Figure 1C and 1D
- Age in months (mouse) and age in years (non-human primate, NHP); RY refers to reproductively young 6-12 wks
- % multinucleated giant cell (MNGC) area
- Figure 4F
- % CD4 positive area
- Animal number, mouse
- Figure 4G and 4H
- % CD3 (4G) and % CD4 (4H) postitive area
- Ovarian structure (corpora lutea, CL; stroma; multinucleated giant cell, MNGC)
Access information
Other publicly accessible locations of the data:
- The RNA sequencing data can be accessed at GEO Accession: GSE283393