Literature Sharing: Biological Characteristics and Diversity of Glomerular Parietal Epithelial Cells

1. Research Background: The Emerging Role of PECs in Kidney Disease

Glomerular parietal epithelial cells (PECs) are a layer of flattened epithelial cells lining the Bowman's capsule (glomerular capsule). Derived from the same cell lineage as podocytes, PECs are adjacent to podocytes in the mature kidney and are highly concerned "precursor cells" with the potential to differentiate into podocytes. Podocytes are key components of the glomerular filtration barrier, and their damage or loss is closely associated with the occurrence and progression of various glomerular diseases. In numerous previous studies, PECs have been found to be closely related to the formation of crescentic glomerulonephritis, a severe type of glomerular disease with rapid progression and poor prognosis. However, the heterogeneity of PECs, their specific subpopulations, and the molecular mechanisms underlying their activation and proliferation in disease states have long remained unclear, limiting the development of targeted therapeutic strategies for related kidney diseases.

2. Core Research: Single-Cell Landscape Reveals the Diversity of PECs

To address these key scientific questions, on April 23, 2023, Professor Anlong Xu's team from Beijing University of Chinese Medicine published an online research paper entitled "Single cell landscape of parietal epithelial cells in healthy and diseased states" in Kidney International, an authoritative journal in nephrology. This study is the first to establish a single-cell atlas of glomerular PECs, which has profoundly advanced the understanding of the heterogeneity and biology of glomerular PECs.

The research team employed a combination of single-cell transcriptome analysis and histopathological staining techniques to conduct in-depth studies on PECs. Single-cell RNA sequencing analysis revealed the diversity of PEC populations, identifying multiple distinct PEC subpopulations, including podocyte progenitors, common PECs, PECs with enhanced collagen fibril organization, PECs transitioning into tubule cells and/or proliferative PECs, and proliferative PECs in crescentic glomerulonephritis (as shown in the figure: Single-cell RNA sequencing analysis reveals the diversity of PEC populations).

Notably, the study identified podocyte precursor cells from PEC subpopulations, clarifying the potential of PECs to differentiate into podocytes. Furthermore, the research team revealed the molecular mechanisms underlying PEC activation and proliferation, which play a crucial role in the occurrence and development of crescentic glomerulonephritis. Based on these findings, the team further screened target proteins Mif and Csf1r that can block the formation of glomerular crescents, and verified the inhibitory effect of targeted inhibitors caffeic acid and Sotuletinib on crescentic glomerular formation in animal experiments, providing new ideas for the clinical treatment of crescentic glomerulonephritis.

3. Technical Support: Multiplex Fluorescence IHC Validates Research Findings

In this study, multiplex fluorescence immunohistochemistry (mIHC) staining technology played a key role in validating the results of single-cell analysis at the tissue level. The research team used mIHC to detect the co-expression of Ki67 (proliferation marker), CD44, SOX9, and DNA in PECs (as shown in the figure: Multiplex fluorescence IHC staining further confirms the results of single-cell analysis at the tissue level).

This technical approach enabled the simultaneous detection of multiple molecular markers in the same tissue section, preserving the spatial context of cell subpopulations and molecular expression, and providing direct histopathological evidence for the identification of PEC subpopulations and the verification of their biological characteristics. The reliability and accuracy of the research findings thus rely heavily on the high performance of mIHC technology, including high sensitivity, specificity, and multi-target detection capability.

4. Absin One-Stop Solution for Multiplex Fluorescence IHC

The successful validation of PEC subpopulations and related molecular mechanisms in this study highlights the important role of high-quality multiplex fluorescence IHC technology in kidney disease research. Absin, a professional sub-brand of ANT BIO PTE. LTD. focusing on general reagents and kits, provides a one-stop solution for multiplex fluorescence IHC, perfectly supporting such in-depth scientific research.

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5. References

1.       Xue RQ. Research progress on the differentiation of glomerular parietal epithelial cells into podocytes as precursor cells [J]. Journal of Clinical and Pathological Research, 2018, 38(6):7. DOI:10.3978/j.issn.2095-6959.2018.06.030.

2.       Liu WB, Huang GR, Liu BL, Hu HK, Geng J, Rui HL, Gao C, Huang YJ, Huo GY, Mao JR, Lu CJ, Xu AL. Single cell landscape of parietal epithelial cells in healthy and diseased states. Kidney Int. 2023 Jul;104(1):108-123. doi: 10.1016/j.kint.2023.03.036. Epub 2023 Apr 24. PMID: 37100348.