The miR-183/96/182 cluster is a checkpoint for resident immune cells and shapes the cellular landscape of the cornea
Copyright © 2023 Elsevier Inc. All rights reserved..
PURPOSE: The conserved miR-183/96/182 cluster (miR-183C) regulates both corneal sensory innervation and corneal resident immune cells (CRICs). This study is to uncover its role in CRICs and in shaping the corneal cellular landscape at a single-cell (sc) level.
METHODS: Corneas of naïve, young adult [2 and 6 months old (mo)], female miR-183C knockout (KO) mice and wild-type (WT) littermates were harvested and dissociated into single cells. Dead cells were removed using a Dead Cell Removal kit. CD45+ CRICs were enriched by Magnetic Activated Cell Sorting (MACS). scRNA libraries were constructed and sequenced followed by comprehensive bioinformatic analyses.
RESULTS: The composition of major cell types of the cornea stays relatively stable in WT mice from 2 to 6 mo, however the compositions of subtypes of corneal cells shift with age. Inactivation of miR-183C disrupts the stability of the major cell-type composition and age-related transcriptomic shifts of subtypes of corneal cells. The diversity of CRICs is enhanced with age. Naïve mouse cornea contains previously-unrecognized resident fibrocytes and neutrophils. Resident macrophages (ResMφ) adopt cornea-specific function by expressing abundant extracellular matrix (ECM) and ECM organization-related genes. Naïve cornea is endowed with partially-differentiated proliferative ResMφ and contains microglia-like Mφ. Resident lymphocytes, including innate lymphoid cells (ILCs), NKT and γδT cells, are the major source of innate IL-17a. miR-183C limits the diversity and polarity of ResMφ.
CONCLUSION: miR-183C serves as a checkpoint for CRICs and imposes a global regulation of the cellular landscape of the cornea.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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| Enthalten in: |
The ocular surface - 30(2023) vom: 12. Okt., Seite 17-41 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Weifeng [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.12.2023 Date Revised 18.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jtos.2023.07.012 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 100 | 1 | |a Li, Weifeng |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The miR-183/96/182 cluster is a checkpoint for resident immune cells and shapes the cellular landscape of the cornea |
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| 500 | |a Date Revised 18.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Elsevier Inc. All rights reserved. | ||
| 520 | |a PURPOSE: The conserved miR-183/96/182 cluster (miR-183C) regulates both corneal sensory innervation and corneal resident immune cells (CRICs). This study is to uncover its role in CRICs and in shaping the corneal cellular landscape at a single-cell (sc) level | ||
| 520 | |a METHODS: Corneas of naïve, young adult [2 and 6 months old (mo)], female miR-183C knockout (KO) mice and wild-type (WT) littermates were harvested and dissociated into single cells. Dead cells were removed using a Dead Cell Removal kit. CD45+ CRICs were enriched by Magnetic Activated Cell Sorting (MACS). scRNA libraries were constructed and sequenced followed by comprehensive bioinformatic analyses | ||
| 520 | |a RESULTS: The composition of major cell types of the cornea stays relatively stable in WT mice from 2 to 6 mo, however the compositions of subtypes of corneal cells shift with age. Inactivation of miR-183C disrupts the stability of the major cell-type composition and age-related transcriptomic shifts of subtypes of corneal cells. The diversity of CRICs is enhanced with age. Naïve mouse cornea contains previously-unrecognized resident fibrocytes and neutrophils. Resident macrophages (ResMφ) adopt cornea-specific function by expressing abundant extracellular matrix (ECM) and ECM organization-related genes. Naïve cornea is endowed with partially-differentiated proliferative ResMφ and contains microglia-like Mφ. Resident lymphocytes, including innate lymphoid cells (ILCs), NKT and γδT cells, are the major source of innate IL-17a. miR-183C limits the diversity and polarity of ResMφ | ||
| 520 | |a CONCLUSION: miR-183C serves as a checkpoint for CRICs and imposes a global regulation of the cellular landscape of the cornea | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Corneal resident fibrocytes (CRFs) | |
| 650 | 4 | |a Corneal resident immune cells (CRICs) | |
| 650 | 4 | |a Corneal resident lymphocytes (CRL) | |
| 650 | 4 | |a Corneal resident myeloid cells (CRMCs) | |
| 650 | 4 | |a Corneal resident neutrophils (CRNs) | |
| 650 | 4 | |a Resident macrophages (ResMφ) | |
| 650 | 4 | |a Single cell RNA sequencing (scRNA seq) | |
| 650 | 4 | |a miR-183/96/182 cluster (miR-183C) | |
| 650 | 4 | |a microRNAs (miRNAs) | |
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| 650 | 7 | |a Mirn96 microRNA, mouse |2 NLM | |
| 650 | 7 | |a Mirn182 microRNA, mouse |2 NLM | |
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| 700 | 1 | |a Hazlett, Linda D |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Shunbin |e verfasserin |4 aut | |
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