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Urine Single-Cell RNA Sequencing in Focal Segmental Glomerulosclerosis Reveals Inflammatory Signatures
INTRODUCTION: Individuals with focal segmental glomerular sclerosis (FSGS) typically undergo kidney biopsy only once, which limits the ability to characterize kidney cell gene expression over time. METHODS: We used single-cell RNA sequencing (scRNA-seq) to explore disease-related molecular signature...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8821042/ https://www.ncbi.nlm.nih.gov/pubmed/35155868 http://dx.doi.org/10.1016/j.ekir.2021.11.005 |
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author | Latt, Khun Zaw Heymann, Jurgen Jessee, Joseph H. Rosenberg, Avi Z. Berthier, Celine C. Arazi, Arnon Eddy, Sean Yoshida, Teruhiko Zhao, Yongmei Chen, Vicky Nelson, George W. Cam, Margaret Kumar, Parimal Mehta, Monika Kelly, Michael C. Kretzler, Matthias Ray, Patricio E. Moxey-Mims, Marva Gorman, Gregory H. Lechner, Brent L. Regunathan-Shenk, Renu Raj, Dominic S. Susztak, Katalin Winkler, Cheryl A. Kopp, Jeffrey B. |
author_facet | Latt, Khun Zaw Heymann, Jurgen Jessee, Joseph H. Rosenberg, Avi Z. Berthier, Celine C. Arazi, Arnon Eddy, Sean Yoshida, Teruhiko Zhao, Yongmei Chen, Vicky Nelson, George W. Cam, Margaret Kumar, Parimal Mehta, Monika Kelly, Michael C. Kretzler, Matthias Ray, Patricio E. Moxey-Mims, Marva Gorman, Gregory H. Lechner, Brent L. Regunathan-Shenk, Renu Raj, Dominic S. Susztak, Katalin Winkler, Cheryl A. Kopp, Jeffrey B. |
author_sort | Latt, Khun Zaw |
collection | PubMed |
description | INTRODUCTION: Individuals with focal segmental glomerular sclerosis (FSGS) typically undergo kidney biopsy only once, which limits the ability to characterize kidney cell gene expression over time. METHODS: We used single-cell RNA sequencing (scRNA-seq) to explore disease-related molecular signatures in urine cells from subjects with FSGS. We collected 17 urine samples from 12 FSGS subjects and captured these as 23 urine cell samples. The inflammatory signatures from renal epithelial and immune cells were evaluated in bulk gene expression data sets of FSGS and minimal change disease (MCD) (The Nephrotic Syndrome Study Network [NEPTUNE] study) and an immune single-cell data set from lupus nephritis (Accelerating Medicines Partnership). RESULTS: We identified immune cells, predominantly monocytes, and renal epithelial cells in the urine. Further analysis revealed 2 monocyte subtypes consistent with M1 and M2 monocytes. Shed podocytes in the urine had high expression of marker genes for epithelial-to-mesenchymal transition (EMT). We selected the 16 most highly expressed genes from urine immune cells and 10 most highly expressed EMT genes from urine podocytes as immune signatures and EMT signatures, respectively. Using kidney biopsy transcriptomic data from NEPTUNE, we found that urine cell immune signature and EMT signature genes were more highly expressed in FSGS biopsies compared with MCD biopsies. CONCLUSION: The identification of monocyte subsets and podocyte expression signatures in the urine samples of subjects with FSGS suggests that urine cell profiling might serve as a diagnostic and prognostic tool in nephrotic syndrome. Furthermore, this approach may aid in the development of novel biomarkers and identifying personalized therapies targeting particular molecular pathways in immune cells and podocytes. |
format | Online Article Text |
id | pubmed-8821042 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-88210422022-02-11 Urine Single-Cell RNA Sequencing in Focal Segmental Glomerulosclerosis Reveals Inflammatory Signatures Latt, Khun Zaw Heymann, Jurgen Jessee, Joseph H. Rosenberg, Avi Z. Berthier, Celine C. Arazi, Arnon Eddy, Sean Yoshida, Teruhiko Zhao, Yongmei Chen, Vicky Nelson, George W. Cam, Margaret Kumar, Parimal Mehta, Monika Kelly, Michael C. Kretzler, Matthias Ray, Patricio E. Moxey-Mims, Marva Gorman, Gregory H. Lechner, Brent L. Regunathan-Shenk, Renu Raj, Dominic S. Susztak, Katalin Winkler, Cheryl A. Kopp, Jeffrey B. Kidney Int Rep Translational Research INTRODUCTION: Individuals with focal segmental glomerular sclerosis (FSGS) typically undergo kidney biopsy only once, which limits the ability to characterize kidney cell gene expression over time. METHODS: We used single-cell RNA sequencing (scRNA-seq) to explore disease-related molecular signatures in urine cells from subjects with FSGS. We collected 17 urine samples from 12 FSGS subjects and captured these as 23 urine cell samples. The inflammatory signatures from renal epithelial and immune cells were evaluated in bulk gene expression data sets of FSGS and minimal change disease (MCD) (The Nephrotic Syndrome Study Network [NEPTUNE] study) and an immune single-cell data set from lupus nephritis (Accelerating Medicines Partnership). RESULTS: We identified immune cells, predominantly monocytes, and renal epithelial cells in the urine. Further analysis revealed 2 monocyte subtypes consistent with M1 and M2 monocytes. Shed podocytes in the urine had high expression of marker genes for epithelial-to-mesenchymal transition (EMT). We selected the 16 most highly expressed genes from urine immune cells and 10 most highly expressed EMT genes from urine podocytes as immune signatures and EMT signatures, respectively. Using kidney biopsy transcriptomic data from NEPTUNE, we found that urine cell immune signature and EMT signature genes were more highly expressed in FSGS biopsies compared with MCD biopsies. CONCLUSION: The identification of monocyte subsets and podocyte expression signatures in the urine samples of subjects with FSGS suggests that urine cell profiling might serve as a diagnostic and prognostic tool in nephrotic syndrome. Furthermore, this approach may aid in the development of novel biomarkers and identifying personalized therapies targeting particular molecular pathways in immune cells and podocytes. Elsevier 2021-11-25 /pmc/articles/PMC8821042/ /pubmed/35155868 http://dx.doi.org/10.1016/j.ekir.2021.11.005 Text en © 2021 Published by Elsevier, Inc., on behalf of the International Society of Nephrology. https://creativecommons.org/licenses/by-nc-nd/3.0/igo/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/igo/). |
spellingShingle | Translational Research Latt, Khun Zaw Heymann, Jurgen Jessee, Joseph H. Rosenberg, Avi Z. Berthier, Celine C. Arazi, Arnon Eddy, Sean Yoshida, Teruhiko Zhao, Yongmei Chen, Vicky Nelson, George W. Cam, Margaret Kumar, Parimal Mehta, Monika Kelly, Michael C. Kretzler, Matthias Ray, Patricio E. Moxey-Mims, Marva Gorman, Gregory H. Lechner, Brent L. Regunathan-Shenk, Renu Raj, Dominic S. Susztak, Katalin Winkler, Cheryl A. Kopp, Jeffrey B. Urine Single-Cell RNA Sequencing in Focal Segmental Glomerulosclerosis Reveals Inflammatory Signatures |
title | Urine Single-Cell RNA Sequencing in Focal Segmental Glomerulosclerosis Reveals Inflammatory Signatures |
title_full | Urine Single-Cell RNA Sequencing in Focal Segmental Glomerulosclerosis Reveals Inflammatory Signatures |
title_fullStr | Urine Single-Cell RNA Sequencing in Focal Segmental Glomerulosclerosis Reveals Inflammatory Signatures |
title_full_unstemmed | Urine Single-Cell RNA Sequencing in Focal Segmental Glomerulosclerosis Reveals Inflammatory Signatures |
title_short | Urine Single-Cell RNA Sequencing in Focal Segmental Glomerulosclerosis Reveals Inflammatory Signatures |
title_sort | urine single-cell rna sequencing in focal segmental glomerulosclerosis reveals inflammatory signatures |
topic | Translational Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8821042/ https://www.ncbi.nlm.nih.gov/pubmed/35155868 http://dx.doi.org/10.1016/j.ekir.2021.11.005 |
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