{"doi":"10.1101/2020.09.03.281733","title":"Detection of infiltrating fibroblasts by single-cell transcriptomics in human kidney allografts","abstract":"Abstract 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 endothelial cells that expressed T-cell chemoattractant cytokines. 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":121077,"datarank":0.4669212848231901,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.13733759822275715,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.13733759822275715,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":6,"citers_with_citation_signal":6,"citers_with_endowment":6,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9224,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":333460,"name":"Hua Yang","orcid":"0000-0003-4993-7796","position":1,"is_corresponding":false},{"id":333461,"name":"Michelle Lubetzky","orcid":"0000-0003-1076-7953","position":2,"is_corresponding":false},{"id":226751,"name":"Pavel Morozov","orcid":"0000-0001-7085-9134","position":3,"is_corresponding":false},{"id":561066,"name":"Mila Lagman","orcid":null,"position":4,"is_corresponding":false},{"id":560126,"name":"Gaurav Thareja","orcid":"0000-0003-2277-6400","position":5,"is_corresponding":false},{"id":80325,"name":"Alicia Alonso","orcid":"0000-0002-2730-7470","position":6,"is_corresponding":false},{"id":560127,"name":"Carol Li","orcid":"0000-0002-0576-2181","position":7,"is_corresponding":false},{"id":335391,"name":"Catherine Snopkowski","orcid":null,"position":8,"is_corresponding":false},{"id":561067,"name":"Aziz Belkadi","orcid":null,"position":9,"is_corresponding":false},{"id":333466,"name":"Franco B. Mueller","orcid":"0000-0002-0304-1268","position":10,"is_corresponding":false},{"id":333463,"name":"John R. Lee","orcid":"0000-0002-9612-5742","position":11,"is_corresponding":false},{"id":271000,"name":"Darshana M. Dadhania","orcid":"0000-0002-7973-1521","position":12,"is_corresponding":false},{"id":105524,"name":"Steven Salvatore","orcid":"0000-0001-7237-2696","position":13,"is_corresponding":false},{"id":288740,"name":"Surya V. Seshan","orcid":"0000-0003-4384-0694","position":14,"is_corresponding":false},{"id":333465,"name":"Vijay K. 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