ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: 0839

Single-Cell Transcriptomics of Mouse and Human Lupus Nephritis Identifies Conserved Myeloid Populations Across Species

Paul Hoover1, Michael Peters2, David Lieb3, Rakesh Mishra4, Nir Hacohen2 and Anne Davidson5, 1Brigham and Women's Hospital, Boston, MA, 2Broad Institute, Boston, 3Broad Institute, Boston, MA, 4Feinstein Institute, Manhasset, NY, 5Northwell Health, New York

Meeting: ACR Convergence 2020

Keywords: Dendritic cells, genomics, Lupus nephritis, macrophages, Mouse

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print
Session Information

Date: Saturday, November 7, 2020

Title: SLE – Animal Models Poster

Session Type: Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: We recently identified novel immune cell states in the kidneys of lupus nephritis patients (Arazi et al, Nature Immunology 2019). To determine the similarities with lupus mouse models, we compared human immune cell transcriptomes to those from Sle1.Yaa and NZBW mouse kidneys. We focused on macrophages and DCs since intrarenal myeloid abundance may drive tissue damage in lupus patients.

Methods: We collected myeloid cells from dissociated kidneys from pre- and post-nephritic Sle1.Yaa and NZBW mice (3-4 mice per group). Using 10x Genomics we performed single cell transcriptomic profiling and analyzed droplets that contained >500 genes and UMIs after doublet removal. To identify intrarenal mouse immune cells equivalent to those in humans, we leveraged immune cell transcriptomes collected from the kidneys of lupus patients in AMP Phase 1 to generate state-specific gene signatures from each human myeloid cell cluster composed of: (i) the top 10 to 40 most highly and ubiquitously differentially expressed (DE) genes, (ii) the top 4-10 DE transcription factors, or (iii) modules of co-varying genes from non-negative matrix factorization. After clustering mouse myeloid cells (Seurat v3.0), we calculated the average of the scaled expression for each human signature across mouse clusters to identify those most similar to human. We also calculated the Pearson correlation coefficient between human and mouse clusters using homologous genes with identical names between species.

Results: We mapped gene signatures from the human myeloid states: ‘inflammatory’ macrophages (CM0) that likely enter from blood and transition to ‘phagocytic’ (CM1) and ‘reparative’ (CM4) states; resident macrophages (CM2); dendritic cells (CM3). We identified the human CM0 signature in clusters from NZBW (and weakly in Sle1.Yaa) post-nephritic pro-inflammatory macrophage/DC clusters that infiltrate from blood, similar to CM0 cells in humans. The human CM1 signature mapped to clusters in both mouse models that resembled DCs and that were enriched for transendothelial migration. We identified in both models the CM4 signature in pre- and post-nephritic mouse clusters that resembled resident macrophages and were enriched for antigen presentation and lysosomal processing. Like humans, the post-nephritic CM4 mouse equivalent cluster exclusively expressed Ccl8, a leukocyte chemoattractant and activator, and Gas6, a mediator of apoptotic cell clearance and was skewed towards an alternative phenotype. Finally, we mapped the human CM3 signature to mouse CD103+ DCs and identified gene programs shared with humans for immunoregulation and antigen presentation.

Conclusion:

From the kidneys of Sle1.Yaa and NZBW mice we identified human myeloid gene signatures: ‘inflammatory’ macrophages (CM0), ‘phagocytic’ (CM1), ‘reparative’ (CM4) states; dendritic cells (CM3); we did not find the human resident macrophage (CM2) signature. We identified putative functions shared between mouse and human clusters including antigen presentation, phagocytosis, Ccl8 expression. These analyses indicate that we may be able to study in mice some of the myeloid subsets and genes that are highly relevant to human disease.


Disclosure: P. Hoover, None; M. Peters, None; D. Lieb, None; R. Mishra, None; N. Hacohen, None; A. Davidson, None.

To cite this abstract in AMA style:

Hoover P, Peters M, Lieb D, Mishra R, Hacohen N, Davidson A. Single-Cell Transcriptomics of Mouse and Human Lupus Nephritis Identifies Conserved Myeloid Populations Across Species [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/single-cell-transcriptomics-of-mouse-and-human-lupus-nephritis-identifies-conserved-myeloid-populations-across-species/. Accessed .
  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

« Back to ACR Convergence 2020

ACR Meeting Abstracts - https://acrabstracts.org/abstract/single-cell-transcriptomics-of-mouse-and-human-lupus-nephritis-identifies-conserved-myeloid-populations-across-species/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology