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Guided Differentiation of Mature Kidney Podocytes from Human Induced Pluripotent Stem Cells Under Chemically Defined Conditions
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Membranous Nephropathy Target Antigens Display Podocyte-Specific and Non-Specific Expression in Healthy Kidneys

Ying Dong1,2,3, Hui Xu4, Damu Tang1,2,3

  • 1Department of Surgery, McMaster University, Hamilton, ON L8S 1C7, Canada.

Genes
|March 28, 2025
PubMed
Abstract

Insights

Most membranous nephropathy target antigens are present in podocytes, with PLA2R1 being a key marker in adult kidney disease. SEMA3B is identified as a potential childhood MNTAg.

Area of Science:

  • Nephrology
  • Immunology
  • Genomics

Background:

  • Autoimmunity against podocyte antigens is a primary cause of membranous nephropathy (MN).
  • Numerous MN target antigens (MNTAgs) have been identified, but their expression in podocytes remains largely uncharacterized.
  • Understanding podocyte expression of MNTAgs is crucial for diagnosing and treating MN.

Purpose of the Study:

  • To investigate the expression patterns of known MNTAgs in adult, fetal, and mouse podocytes.
  • To identify potential MNTAgs relevant to different age groups and species.
  • To correlate MNTAg expression with podocyte injury and disease states.

Main Methods:

  • Utilized CZ CELLxGene single-cell RNA sequencing datasets from adult, fetal, and mouse kidneys.
  • Analyzed the expression of a comprehensive list of MNTAgs, including PLA2R1, THSD7A, and others.
  • Examined chromatin accessibility data to infer transcriptional regulation of MNTAg expression.

Main Results:

  • Most MNTAgs are expressed in adult podocytes, with PLA2R1 showing significantly higher enrichment and acting as a major podocyte marker.
  • PLA2R1 is upregulated in podocytes across various kidney diseases associated with proteinuria.
  • SEMA3B is highly expressed in fetal podocytes, suggesting its role as a childhood MNTAg, while Thsd7a is prominent in mouse podocytes.

Conclusions:

  • The majority of MNTAgs are expressed in podocytes during both adult life and renal development.
  • PLA2R1 is a critical podocyte marker in adults, with its elevated expression linked to kidney diseases and proteinuria.
  • Specific MNTAgs like SEMA3B and Thsd7a show distinct expression patterns in fetal and mouse kidneys, respectively, highlighting species- and developmental-specific roles.
Keywords:
MN target antigensmembranous nephropathypodocytesingle-cell RNA sequencing

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