HCA Data Explorer

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

Updated February 17, 2023

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.

Hemant SuryawanshiThe Rockefeller Universityhsuryawans@rockefeller.edu
Thomas TuschlThe Rockefeller Universityttuschl@rockefeller.edu
Thangamani MuthukumarWeill Cornell Medical Collegemut9002@med.cornell.edu
Hemant Suryawanshi1
Hua Yang2
Michelle Lubetzky2
Pavel Morozov1
Mila Lagman2
Gaurav Thareja3
Alicia Alonso2
Carol Li2
Catherine Snopkowski2
Aziz Belkadi3
Franco B Mueller2
John R Lee2
Darshana M Dadhania2
Steven P Salvatore2
Surya V Seshan2
Vijay K Sharma2
Karsten Suhre3
Manikkam Suthanthiran2
Thomas Tuschl1
Thangamani Muthukumar2
1The Rockefeller University
2Weill Cornell Medical College
3Weill Cornell Medical College in Qatar
Ida Zucchi

To reference this project, please use the following link:

https://explore.data.humancellatlas.org/projects/6e522b93-9b70-4f0c-9990-b9cff721251b
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Analysis Portals

None

Project Label

SuryawanshiKidneyAllografts

Species

Homo sapiens

Sample Type

specimens

Anatomical Entity

kidney

Organ Part

Unspecified

Selected Cell Types

Unspecified

Disease Status (Specimen)

2 disease statuses

Disease Status (Donor)

7 disease statuses

Development Stage

human adult stage

Library Construction Method

10x 3' v2

Nucleic Acid Source

single cell

Paired End

false

Analysis Protocol

matrix_generation

File Format

3 file formats

Cell Count Estimate

7.2k

Donor Count

3
fastq.gz6 file(s)txt.gz3 file(s)xlsx2 file(s)