Spatial Location Determines Cell Fate: Single-Cell Spatial Transcriptomics Reveals the "Social Network" of PT_VCAM1 Cells in Lupus Nephritis
Release date : Sep 02,2026
Classification : Blog
Spatial Location Determines Cell Fate: Single-Cell Spatial Transcriptomics Reveals the "Social Network" of PT_VCAM1 Cells in Lupus Nephritis
For Research Use Only. Not for use in diagnostic procedures.
Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE), characterized by immune cell infiltration, tubular epithelial injury, and progressive fibrosis. While single-cell RNA sequencing has identified key immune subpopulations in LN — such as granzyme K⁺ CD8 T cells and CD163⁺ dendritic cells — the role of tubular epithelial subpopulations, particularly proximal tubule (PT) cells, has remained insufficiently explored. PT cells are essential for kidney function and exhibit subpopulation-specific heterogeneity in disease, but how their spatial arrangement drives the inflammatory-fibrotic microenvironment is poorly understood.
The spatial resolution bottleneck
Prior studies could identify cell types and gene expression changes, but could not answer a fundamental question: which cells are physically interacting, and where? Spot-based spatial transcriptomics reveals tissue-level niches but mixes signals from multiple cells per spot. mIHC confirms protein-level proximity but lacks transcriptome-wide resolution. Neither can trace a specific gene's expression to a specific cell at a defined spatial position — the evidence gap that this study aimed to close.
A 2025 study published in Annals of the Rheumatic Diseases by a team at the University of Science and Technology of China (Kun Qu, Chuang Guo, Guosheng Wang) set out to address this gap. Their multi-modal approach — integrating snRNA-seq, snATAC-seq, spot-based Visium spatial transcriptomics, and mIHC — identified a pathological niche (niche 5) in the LN renal cortex enriched with PT_VCAM1 cells, myofibroblasts, and immune cells. To validate their colocalization at true single-cell resolution, the team turned to SeekSpace™.
SeekSpace™: Single-Cell Resolution, In Situ
SeekSpace™ labels every nucleus in a tissue section with a spatial barcode, followed by single-nucleus sequencing — enabling each transcript read to be associated with an individual nucleus and its precise tissue coordinate.
| Challenge with Spot-Based ST | What SeekSpace™ Enables |
|---|---|
| Mixed signals per spot require deconvolution | Cell types identified directly from single-nucleus transcriptomes |
| Gene expression cannot be traced to a specific cell | Every signal mapped to its nucleus and spatial position |
| Rare cells may be masked by abundant neighbours | Rare subpopulations detected independently |
| Cell-cell distances are approximated | Interaction analysis at true single-cell precision |
Proof in the Paper: SeekSpace™ in Action
In this study, SeekSpace™ was applied to LN kidney biopsy samples and delivered two key results:
1. Confirmed single-cell colocalization in niche 5
SeekSpace™ mapped 27 of 35 cell subpopulations to kidney tissue and provided direct single-cell resolution evidence that PT_VCAM1 cells, myofibroblasts, and immune cells spatially co-aggregate in the cortical region — complementing the spot-level and mIHC findings.
2. Validated cell-type-specific gene expression in situ
SeekSpace™ data confirmed high COL4A1 expression in PT_VCAM1 cells, supporting the hypothesis that a disease-risk variant (rs4284503) drives aberrant collagen deposition through this specific cell type — a distinction that mixed-spot data alone could not resolve.
Why It Matters
This study illustrates a pattern researchers increasingly encounter: spot-level spatial data identifies the neighborhood; single-cell spatial data identifies the neighbors.
Complementary resolution layers
Spot-based spatial transcriptomics (e.g., 10x Visium) provides valuable tissue-level mapping and niche identification. Single-cell spatial transcriptomics (SeekSpace™) adds a complementary layer — resolving who is where, tracing gene expression to specific cells, and enabling distance-based interaction screening. Together, they provide a more complete picture of tissue biology.
For studies involving rare cell populations, cell-type-specific gene regulation, or micrometer-scale cell-cell interactions, SeekSpace™ provides the resolution layer that bridges the gap between "where" and "who."
Reference
Wang J, Zheng A, Liu N, et al. Integrative spatial multiomics analysis reveals regulatory mechanisms of VCAM1⁺ proximal tubule cells in lupus nephritis. Ann Rheum Dis. 2025;84:2021-2033. https://doi.org/10.1016/j.ard.2025.08.015
Contact
For more information about SeekSpaceTM , please contact us at:
info@seekgene.com
For Research Use Only. Not for use in diagnostic procedures.
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