Abstract: SA-PO1041
Single-Cell Transcriptome Atlas in C57BL/6 Mice Encodes Morphological Phenotypes in the Aging Kidneys
Session Information
- Pathology and Lab Medicine - II
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pathology and Lab Medicine
- 1800 Pathology and Lab Medicine
Author
- Yang, Shanzhi, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
Background
C57BL/6 mice are commonly used murine models with the desired genetic background for modification in different research settings. So far, there is still a lack of comprehensive kidney morphology and single-cell transcriptome atlas at various developmental stages of C57BL/6 mice. To provide an interactive set of reference standards for the scientific community, we designed the present study to dissect the kidney from the capillary-loop stage of development till senescence at 30 months of age.
Methods
Eight groups, with five to six mice each, represented embryonic (18.5 days), newborn (1 day), adolescent (1 month), young (3 months), adulthood (6 months), middle-aged (10 months), old (20 months), and senescent (30 months) animals, respectively. Periodic acid-Schiff and silver staining were used to examine the histology of the kidney. The ultrastructure features of the kidney were examined using transmission electron microscopy. Kidney single-cell transcriptome analysis was conducted in three and 30 month-old mice to reveal the gene expression profiles in glomerular cells. Unbiased sampling and quantitation method was used to analyze the glomerular structures.
Results
With age, there was an increase in the glomerular size, the percentage of podocyte foot process effacement, and the extent of mesangial expansion. The number of Wilm’s tumor 1 (WT1) positive podocytes remained stable from the young till 20 months of age. By age 20 months, the number of WT1 positive podocytes was reduced till 30 months of age. Of note, GBM knobs appeared at three months and became frequent with age. The level of urinary albumin to creatinine ratio (UACR) was increased in the senescent mice compared with the maturing and middle-aged mice. Using single-cell transcriptomic data, we assessed cell-type-specific manifestations of different hallmarks of aging, such as changes in the genes of intrinsic renal cells and biological alterations involved with age.
Conclusion
In conclusion, the availability of comprehensive kidney morphology and single-cell transcriptome atlas at various developmental stages of C57BL/6 mice would be a new and significant resource for mechanistic investigations and testing of potential therapeutic interventions.
Funding
- Government Support – Non-U.S.