{
  "abstract": "Purpose: To investigate the cellular dynamics of androgen-deficient meibomian gland dysfunction (MGD) and to elucidate the molecular mechanisms limiting the structural regenerative efficacy of topical dihydrotestosterone (DHT) treatment.\n\nMethods: Single-cell RNA sequencing (scRNA-seq) was performed on meibomian glands from sham-operated controls, castrated mice, and castrated mice receiving topical 0.08% DHT. We performed comparative analyses to quantify changes in cell composition, reconstruct differentiation trajectories, and systematically profile alterations in metabolic pathways and organelle homeostasis networks.\n\nResults: Castration arrested meibocyte differentiation and redirected cell fate commitment. Pseudotime trajectory analysis revealed a pronounced shift from the meibocyte lineage toward ductal and progenitor fates, accompanied by comprehensive downregulation of lipogenic genes (e.g., Fasn, Awat2). This fate reprogramming was coupled with disrupted endoplasmic reticulum (ER) homeostasis, including suppression of the ER membrane protein complex (EMC) and impaired lipid assembly machinery. Topical DHT treatment partially restored meibocyte differentiation but failed to fully recover gland morphology. Furthermore, rapid metabolic reactivation following DHT treatment outpaced ER capacity recovery, inducing proteostatic stress.\n\nConclusions: Androgen deficiency drives MGD through dual mechanisms: reprogramming of meibocyte cell fate toward non-lipogenic lineages and suppression of EMC-mediated stabilization of ER-resident lipogenic enzymes. The resulting temporal mismatch between lipogenic reactivation and ER capacity recovery upon DHT treatment induces proteostatic stress, limiting the efficacy of androgen monotherapy and identifying the EMC–ER axis as a candidate therapeutic target for combinatorial intervention.",
  "abstract_shown": true,
  "affiliations": [
    "State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, China",
    "Ningbo Key Laboratory of Medical Research on Blinding Eye Diseases, Ningbo Eye Institute, Ningbo Eye Hospital, Wenzhou Medical University, Ningbo, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Shenchuan Qian"
    },
    {
      "affs": [
        0
      ],
      "name": "Zihao Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Mike Pan"
    },
    {
      "affs": [
        0
      ],
      "name": "Meiling Zhu"
    },
    {
      "affs": [
        0
      ],
      "name": "Juan Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuyang Fu"
    },
    {
      "affs": [
        0
      ],
      "name": "Qian Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Zhiwei Zha"
    },
    {
      "affs": [
        0
      ],
      "name": "Ying Feng"
    },
    {
      "affs": [
        0
      ],
      "name": "Wei Chen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/05bx4yj9zvb64.bib",
  "cited_by": 0,
  "doi": "10.1167/iovs.67.12.46",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13715919/",
  "id": "05bx4yj9zvb64",
  "issns": [
    "0146-0404",
    "1552-5783"
  ],
  "landing_url": "https://doi.org/10.1167/iovs.67.12.46",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Cornea"
    ],
    [
      "openalex",
      "2739|Ocular Surface and Contact Lens"
    ]
  ],
  "openalex": "W7223174301",
  "pdf_url": null,
  "pmcid": "PMC13715919",
  "pmid": "42910814",
  "published": "2026-10-22",
  "publisher": "Association for Research in Vision and Ophthalmology",
  "ris": "https://research.draconitic.com/paper/05bx4yj9zvb64.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T12:23:06Z",
      "native_id": "PMC13715919",
      "source": "pmc",
      "url": "https://doi.org/10.1167/iovs.67.12.46"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2739|Ocular Surface and Contact Lens",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Single-Cell Sequencing Reveals Androgen Deficiency Arrests Meibocyte Differentiation and Impairs EMC-Mediated Lipid Metabolism",
  "title_text": "Single-Cell Sequencing Reveals Androgen Deficiency Arrests Meibocyte Differentiation and Impairs EMC-Mediated Lipid Metabolism",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:23:06Z",
  "url": "https://research.draconitic.com/paper/05bx4yj9zvb64",
  "venue": "Investigative Ophthalmology & Visual Science",
  "versions": []
}