{"data":{"event":{"id":"83cd7f4f-32d7-45c7-ac18-6a9f1c1eaab8","slug":"a-transcriptional-continuum-from-clinically-normal-to-lesional-skin-sing-71c4cd8198","title":"\n\nA transcriptional continuum from clinically normal to lesional skin: Single-cell trajectory analysis of psoriasis \n\n","short_summary":"Psoriasis is a chronic inflammatory skin disease characterized by immune dysregulation and complex cellular interactions involving keratinocytes (KCs), T cells, and endothelial cells. Single-cell studies have mapped the cellular diversity of psoriatic plaques, yet most analyses treat skin as either healthy or diseased and therefore overlook the graded changes that precede a visible lesion. We asked whether psoriasis instead progresses along a transcriptional continuum and whether clinically normal skin from patients already carries a measurable disease signature. Using single-cell RNA sequenci","full_description":"Psoriasis is a chronic inflammatory skin disease characterized by immune dysregulation and complex cellular interactions involving keratinocytes (KCs), T cells, and endothelial cells. Single-cell studies have mapped the cellular diversity of psoriatic plaques, yet most analyses treat skin as either healthy or diseased and therefore overlook the graded changes that precede a visible lesion. We asked whether psoriasis instead progresses along a transcriptional continuum and whether clinically normal skin from patients already carries a measurable disease signature. Using single-cell RNA sequencing (scRNA-seq) of healthy skin (NS), clinically normal skin adjacent to lesions (PN), and lesional skin (PP), we combined two complementary designs: a complete set spanning all three states and a within-patient paired set of matched PN and PP skin biopsies that removes inter-individual variability. Trajectory analysis using a novel pseudotime approach reveals transcriptional changes within cell populations and dynamic cellular states underlying psoriatic pathology. To distinguish lesion-driven effects from disease-associated transcriptional changes, we applied a differential expression strategy comparing PP and PN psoriatic tissue with NS and integrating these contrasts. This approach enabled the identification of disease-specific gene signatures while minimizing lesion-specific bias. As a result, we identified a coherent, cell-type-resolved continuum of transcriptional states in which endothelial cells, IL20+ keratinocytes (KCs: IL20), and KGF+ keratinocytes (KCs: KGF) undergo trajectory-dependent state transitions. These trajectories converge on features including epidermal thickening, barrier dysfunction, and plaque maintenance. Endothelial cells transition from an inflamed, angiogenic state to a mature, barrier-stabilized phenotype, while KCs: IL20 and KCs: KGF shift from PN states toward hyperproliferative, stress-adapted lesional phenotypes. These findings reframe psoriasis as a dynamic, multicellular continuum and identify candidate temporal windows for early intervention.","ledger_type":"benefit","primary_domain_id":"8f1af1b9-7302-4b51-aae9-fdfac04d158a","event_status":"provisional","event_date":"2026-09-21T00:00:00.000Z","discovery_date":"2026-09-21T00:00:00.000Z","first_published_date":"2026-09-21T00:00:00.000Z","last_reviewed_date":"2026-09-21T00:00:00.000Z","geographic_scope":"International","affected_population":null,"base_impact_tier":1,"base_score":"1.00","attribution_multiplier":"0.1000","evidence_multiplier":"0.1000","realization_multiplier":"0.2000","durability_multiplier":"0.5000","current_event_score":"0.001000","confidence_level":"low","score_explanation":"Auto-published from news ingest as a provisional placeholder. Score is conservative until a named release is identified and the record is rescored.","methodology_version_id":"8745541b-0f8e-4d5a-9b47-5291d3813a8d","original_methodology_version_id":"8745541b-0f8e-4d5a-9b47-5291d3813a8d","published_at":"2026-09-21T16:00:59.422Z","created_at":"2026-09-21T16:00:59.422Z","updated_at":"2026-09-21T16:00:59.422Z","flags":[],"domain_name":"Biology","domain_slug":"biology","methodology_version":"0.2"},"contributions":[{"id":"168426ab-c883-44e9-a3b7-e6d13a4d4479","event_id":"83cd7f4f-32d7-45c7-ac18-6a9f1c1eaab8","model_id":"535014f7-c941-4d39-aa9b-8f9c1d3d07b7","role_description":"Unspecified system mentioned or implied by a news item. Remap to a named release when identified.","attribution_multiplier":"0.1000","credit_share":"1.0000","contribution_score":"0.001000","attribution_rationale":"News ingest does not infer a named model from the publisher alone. Attribution stays unspecified until a release is identified.","attribution_confidence":"medium","first_used_date":"2026-09-21T00:00:00.000Z","model_version_if_known":null,"review_status":"approved","created_at":"2026-09-21T16:00:59.438Z","model_slug":"unspecified-ai-system","model_name":"Unspecified AI system","identity_class":"unknown","is_internal":false,"family_name":"Unspecified","family_slug":"unknown-unspecified","organization_name":"Unknown","organization_slug":"unknown"}],"sources":[{"id":"bd29a700-8d04-4a50-971c-a12e3a6bff04","event_id":"83cd7f4f-32d7-45c7-ac18-6a9f1c1eaab8","url":"\nhttps://www.biorxiv.org/content/10.64898/2026.09.15.751704v1?rss=1\n","canonical_url":"\nhttps://www.biorxiv.org/content/10.64898/2026.09.15.751704v1?rss=1\n","source_type":"preprint","publisher":"bioRxiv","author":null,"publication_date":"2026-09-21T00:00:00.000Z","retrieved_at":"2026-09-21T16:00:59.447Z","title":"\n\nA transcriptional continuum from clinically normal to lesional skin: Single-cell trajectory analysis of psoriasis \n\n","excerpt":"Psoriasis is a chronic inflammatory skin disease characterized by immune dysregulation and complex cellular interactions involving keratinocytes (KCs), T cells, and endothelial cells. Single-cell studies have mapped the cellular diversity of psoriatic plaques, yet most analyses treat skin as either healthy or diseased and therefore overlook the graded changes that precede a visible lesion. We asked whether psoriasis instead progresses along a transcriptional continuum and whether clinically norm","content_hash":null,"source_reliability_class":"medium","is_primary_source":true,"is_independent":true,"is_peer_reviewed":false,"archived_url":null,"created_at":"2026-09-21T16:00:59.447Z"}],"claims":[{"id":"ee0f1f49-b22d-4e35-93a9-1094b5b7fdeb","event_id":"83cd7f4f-32d7-45c7-ac18-6a9f1c1eaab8","claim_text":"\n\nA transcriptional continuum from clinically normal to lesional skin: Single-cell trajectory analysis of psoriasis \n\n","claim_type":"outcome","claim_status":"supported","confidence_score":null,"created_at":"2026-09-21T16:00:59.456Z","updated_at":"2026-09-21T16:00:59.456Z"}],"revisions":[{"id":"47a5869b-fa63-41f5-9276-1c67479fb3c2","event_id":"83cd7f4f-32d7-45c7-ac18-6a9f1c1eaab8","model_id":null,"previous_score":"0.000000","new_score":"0.001000","previous_factors":{},"new_factors":{"tier":1,"evidence":0.1,"base_score":1,"durability":0.5,"attribution":0.1,"realization":0.2},"change_reason":"Auto-published from news ingest.","trigger_type":"news_ingest","trigger_source_ids":null,"reviewer_id":null,"review_status":"published","created_at":"2026-09-21T16:00:59.465Z"}],"secondary":[]},"methodology_version":"0.1"}