| First Author | Li W | Year | 2023 |
| Journal | Ocul Surf | Volume | 30 |
| Pages | 17-41 | PubMed ID | 37536656 |
| Mgi Jnum | J:361402 | Mgi Id | MGI:7857341 |
| Doi | 10.1016/j.jtos.2023.07.012 | Citation | Li W, et al. (2023) The miR-183/96/182 cluster is a checkpoint for resident immune cells and shapes the cellular landscape of the cornea. Ocul Surf 30:17-41 |
| abstractText | 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 naive, 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. Naive mouse cornea contains previously-unrecognized resident fibrocytes and neutrophils. Resident macrophages (ResMphi) adopt cornea-specific function by expressing abundant extracellular matrix (ECM) and ECM organization-related genes. Naive cornea is endowed with partially-differentiated proliferative ResMphi and contains microglia-like Mphi. Resident lymphocytes, including innate lymphoid cells (ILCs), NKT and gammadeltaT cells, are the major source of innate IL-17a. miR-183C limits the diversity and polarity of ResMphi. CONCLUSION: miR-183C serves as a checkpoint for CRICs and imposes a global regulation of the cellular landscape of the cornea. |
