Cell-Type-Specific Complement Expression in the Healthy and Diseased Retina.

Müller cell age-dependent alternative classical complement expression eye ischemia lectin neuron retina

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
26 11 2019
Historique:
received: 11 01 2019
revised: 24 05 2019
accepted: 22 10 2019
entrez: 28 11 2019
pubmed: 28 11 2019
medline: 21 10 2020
Statut: ppublish

Résumé

Complement dysregulation is a feature of many retinal diseases, yet mechanistic understanding at the cellular level is limited. Given this knowledge gap about which retinal cells express complement, we performed single-cell RNA sequencing on ∼92,000 mouse retinal cells and validated our results in five major purified retinal cell types. We found evidence for a distributed cell-type-specific complement expression across 11 cell types. Notably, Müller cells are the major contributor of complement activators c1s, c3, c4, and cfb. Retinal pigment epithelium (RPE) mainly expresses cfh and the terminal complement components, whereas cfi and cfp transcripts are most abundant in neurons. Aging enhances c1s, cfb, cfp, and cfi expression, while cfh expression decreases. Transient retinal ischemia increases complement expression in microglia, Müller cells, and RPE. In summary, we report a unique complement expression signature for murine retinal cell types suggesting a well-orchestrated regulation of local complement expression in the retinal microenvironment.

Identifiants

pubmed: 31775049
pii: S2211-1247(19)31406-8
doi: 10.1016/j.celrep.2019.10.084
pmc: PMC6911814
mid: NIHMS1544713
pii:
doi:

Substances chimiques

Complement System Proteins 9007-36-7

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2835-2848.e4

Subventions

Organisme : NEI NIH HHS
ID : R01 EY030192
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM108600
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM125301
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG006137
Pays : United States

Informations de copyright

Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

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Auteurs

Diana Pauly (D)

Experimental Ophthalmology, University Hospital Regensburg, Regensburg 93053, Germany. Electronic address: diana.pauly@ukr.de.

Divyansh Agarwal (D)

Genomics and Computational Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Nicholas Dana (N)

Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Nicole Schäfer (N)

Experimental Ophthalmology, University Hospital Regensburg, Regensburg 93053, Germany.

Josef Biber (J)

Department of Physiological Genomics, Biomedical Center, Ludwig Maximilians University Munich, Planegg-Martinsried 82152, Germany.

Kirsten A Wunderlich (KA)

Department of Physiological Genomics, Biomedical Center, Ludwig Maximilians University Munich, Planegg-Martinsried 82152, Germany.

Yassin Jabri (Y)

Experimental Ophthalmology, University Hospital Regensburg, Regensburg 93053, Germany.

Tobias Straub (T)

Core Facility Bioinformatics, Biomedical Center, Ludwig Maximilians University Munich, Planegg-Martinsried 82152, Germany.

Nancy R Zhang (NR)

Department of Statistics, The Wharton School, University of Pennsylvania, Philadelphia, PA 19104, USA.

Avneesh K Gautam (AK)

Department of Medicine, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Bernhard H F Weber (BHF)

Institute of Human Genetics, University of Regensburg, Regensburg 93053, Germany.

Stefanie M Hauck (SM)

Research Unit Protein Science, Helmholtz Center Munich, Research Center for Environmental Health (GmbH), Munich 80939, Germany.

Mijin Kim (M)

Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Christine A Curcio (CA)

Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL 35294-0019, USA.

Dwight Stambolian (D)

Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Mingyao Li (M)

Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.

Antje Grosche (A)

Department of Physiological Genomics, Biomedical Center, Ludwig Maximilians University Munich, Planegg-Martinsried 82152, Germany. Electronic address: antje.grosche@med.uni-muenchen.de.

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Classifications MeSH