Single-Cell Transcriptomics of Human Native Kidney and Kidney Allografts and New Insights Into the Mechanism of Fibrosis

Abstract

In order to evaluate whether distinct cell types and states may be identified in human kidney allograft rejection compared to normal kidney, we sequenced 3 kidney biopsies using the 10x Chromium platform and generated 7,217 high-quality single-cell transcriptomes. Taking advantage of the recipient-donor sex mismatches in the allograft biopsies, we unexpectedly observed that in the biopsy with fibrosis, more than half of the kidney allograft fibroblasts were recipient-derived and therefore likely migratory and graft infiltrative, whereas in the biopsy without fibrosis, all the fibroblasts were donor-derived. Furthermore, tubular progenitor cells that overexpress profibrotic extracellular matrix genes potentially contributing to fibrosis, were enriched in the biopsy with fibrosis. In addition, our analysis revealed unique cell types and states in the kidney. Single-cell transcriptomics complemented histopathology and yielded promising mechanistic insights for individualizing the care of transplant recipients and revealed a new approach to study cell migratory contributions in allograft fibrosis.