Details

Autor(en) / Beteiligte

• Hemant Suryawanshi
• Hua Yang
• Michelle Lubetzky
• Pavel Morozov
• Mila Lagman
• Gaurav Thareja
• Alicia Alonso
• Carol Li
• Catherine Snopkowski
• Aziz Belkadi
• Franco B Mueller
• John R Lee
• Darshana M Dadhania
• Steven P Salvatore
• Surya V Seshan
• Vijay K Sharma
• Karsten Suhre
• Manikkam Suthanthiran
• Thomas Tuschl
• Thangamani Muthukumar

Titel

Detection of infiltrating fibroblasts by single-cell transcriptomics in human kidney allografts

Ist Teil von

• PloS one, 2022-01, Vol.17 (6), p.e0267704

Ort / Verlag

Public Library of Science (PLoS)

Erscheinungsjahr

2022

Link zum Volltext

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• We tested the hypothesis that single-cell RNA-sequencing (scRNA-seq) analysis of human kidney allograft biopsies will reveal distinct cell types and states and yield insights to decipher the complex heterogeneity of alloimmune injury. We selected 3 biopsies of kidney cortex from 3 individuals for scRNA-seq and processed them fresh using an identical protocol on the 10x Chromium platform; (i) HK: native kidney biopsy from a living donor, (ii) AK1: allograft kidney with transplant glomerulopathy, tubulointerstitial fibrosis, and worsening graft function, and (iii) AK2: allograft kidney after successful treatment of active antibody-mediated rejection. We did not study T-cell-mediated rejections. We generated 7217 high-quality single cell transcriptomes. Taking advantage of the recipient-donor sex mismatches revealed by X and Y chromosome autosomal gene expression, we determined that in AK1 with fibrosis, 42 months after transplantation, more than half of the kidney allograft fibroblasts were recipient-derived and therefore likely migratory and graft infiltrative, whereas in AK2 without fibrosis, 84 months after transplantation, most fibroblasts were donor-organ-derived. Furthermore, AK1 was enriched for tubular progenitor cells overexpressing profibrotic extracellular matrix genes. AK2, eight months after successful treatment of rejection, contained plasmablast cells with high expression of immunoglobulins, endothelial cell elaboration of T cell chemoattractant cytokines, and persistent presence of cytotoxic T cells. In addition to these key findings, our analysis revealed unique cell types and states in the kidney. Altogether, single-cell transcriptomics yielded novel mechanistic insights, which could pave the way for individualizing the care of transplant recipients.