In this proof-of-concept study, spatial transcriptomics combined with public single-cell RNA sequencing
data were used to explore the potential of this technology to study kidney allograft
rejection. We aimed to map gene expression patterns within diverse pathological states by
examining biopsies classified across non-rejection, T cell-mediated acute rejection, and
interstitial fibrosis and tubular atrophy (IFTA). Our results revealed distinct immune cell
signatures, including those of T and B lymphocytes, monocytes, mast cells, and plasma cells, and
their spatial organization within the renal interstitium. We also mapped chemokine receptors
and ligands to study immune-cell migration and recruitment. Finally, our analysis demonstrated
differential spatial enrichment of transcription signatures associated with kidney allograft
rejection across various biopsy regions. Interstitium regions displayed higher enrichment scores
for rejection-associated gene expression patterns than did tubular areas, which had negative
scores. This implies that these signatures are primarily driven by processes unfolding in the renal
interstitium. Overall, this study highlights the value of spatial transcriptomics for revealing
cellular heterogeneity and immune signatures in renal transplant biopsies, and demonstrates its
potential for studying the molecular and cellular mechanisms associated with rejection.
However, certain limitations must be borne in mind regarding the development and future
applications of this technology.
Overall design: Using spatial transcriptomics, this study examined three kidney post-implantation biopsies with different histological phenotypes. The Banff criteria were used to evaluate the samples. Each sample exhibited different rejection levels with varying parameter scores, including i, t, v, and g. The diagnostic categories for biopsy samples included acute cellular rejection, interstitial fibrosis and tubular atrophy (IFTA), and unaltered (non-rejection).
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