NCoR1 Protects Mice From Dextran Sodium Sulfate-Induced Colitis by Guarding Colonic Crypt Cells From Luminal Insult.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32044398", "kind": "science-record", "revision": 5, "content_hash": "sha256:44884c29cff117b70045b4a0752a1c1844667ba912eab83f3dcb4ec1a1a2153f", "created_at": "2026-11-01T15:40:56Z", "updated_at": "2026-11-01T18:51:57Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "NCoR1 Protects Mice From Dextran Sodium Sulfate-Induced Colitis by Guarding Colonic Crypt Cells From Luminal Insult.", "doi": "10.1016/j.jcmgh.2020.01.014", "pmid": "32044398", "authors": ["Elvira Mennillo", "Xiaojing Yang", "Miles Paszek", "Johan Auwerx", "Christopher Benner", "Shujuan Chen"], "journal": "Cellular and molecular gastroenterology and hepatology", "year": 2020, "abstract": "BACKGROUND & AIMS: Colonic stem cells are essential for producing the mucosal lining, which in turn protects stem cells from insult by luminal factors. Discovery of genetic and biochemical events that control stem cell proliferation and differentiation can be leveraged to decipher the causal factors of ulcerative colitis and aid the development of more effective therapy.\nMETHODS: We performed in vivo and in vitro studies from control (nuclear receptor corepressor 1 [NCoR1F/F]) and intestinal epithelial cell-specific NCoR1-deficient mice (NCoR1ΔIEC). Mice were challenged with dextran sodium sulfate to induce experimental ulcerative colitis, followed by colitis examination, barrier permeability analysis, cell proliferation immunostaining assays, and RNA sequencing analysis. By using crypt cultures, the organoid-forming efficiency, cell proliferation, apoptosis, and histone acetylation were analyzed after butyrate and/or tumor necrosis factor α treatments.\nRESULTS: NCoR1ΔIEC mice showed a dramatic increase in disease severity in this colitis model, with suppression of proliferative cells at the crypt base as an early event and a concomitant increase in barrier permeability. Genome expression patterns showed an important role for NCoR1 in colonic stem cell proliferation and secretory cell differentiation. Colonic organoids cultured from NCoR1ΔIEC mice were more sensitive to butyrate-induced cell growth inhibition and apoptosis, which were exaggerated further by tumor necrosis factor α co-treatment, which was accompanied by increased histone acetylation.\nCONCLUSIONS: NCoR1 regulates colonic stem cell proliferation and secretory cell differentiation. When NCoR1 is disrupted, barrier protection is weakened, allowing luminal products such as butyrate to penetrate and synergistically damage the colonic crypt cells. Transcript profiling: RNA sequencing data have been deposited in the GEO database, accession number: GSE136153.", "claims": [{"id": "claim-data-access", "statement": "Transcript profiling: RNA sequencing data have been deposited in the GEO database, accession number: GSE136153.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32044398", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Transcript profiling: RNA sequencing data have been deposited in the GEO database, accession number: GSE136153."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:32044398"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE136153"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE136153"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32044398", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.jcmgh.2020.01.014", "sha256": "sha256:21780f78dc2297714a450b83a06c849008cb47301aad00d7b69e1731e2e28461", "bytes": 63870, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1016/j.jcmgh.2020.01.014", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7229481", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE136153", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE136153", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE136153", "version": null, "note": "Transcript profiling: RNA sequencing data have been deposited in the GEO database, accession number: GSE136153.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Transcript profiling: RNA sequencing data have been deposited in the GEO database, accession number: GSE136153.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4041706", "GSM4041707", "GSM4041708", "GSM4041709", "GSM4041710", "GSM4041711", "GSM4041712", "GSM4041713", "GSM4041714", "GSM4041715", "GSM4041716", "GSM4041717", "GSM4041718", "GSM4041719", "GSM4041720", "GSM4041721"], "sample_count": 16, "group_sizes": null, "group_sizes_basis": null, "platform": "21103", "taxon": "Mus musculus", "title": "RNA-sequencing study on DSS-induced ulcerative colitis in mice of wild type and intestinal epithelial cell-sepific NCoR1 deletion.", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE136153 not downloaded", "asset:data:geo:GSE136153 licence not read"]}, "analysis": {"state": "absent", "methods": [], "targets": [], "gaps": ["method", "operations"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "blocked", "tier": "R4", "blocking_axis": "method", "blocked_on": "method:not_determinable", "axes": {"method": {"tier": "R4", "expressible": false, "required_operations": [], "missing_operations": [], "basis": "The reader quoted the method the paper names (not named), but the corpus's method extractor could not map it onto a DSL operation, so the method is published but not expressible."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE136153"], "resolved_accessions": ["GSE136153"], "statements": ["Transcript profiling: RNA sequencing data have been deposited in the GEO database, accession number: GSE136153."], "basis": "The paper names GSE136153 in GEO database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:32044398", "data:geo:GSE136153"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE136153"]}, "gaps": ["method:not_determinable"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:56:46Z", "independence": "single_reader"}, "evidence_check": {"method": "absent", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 51870, "completion_tokens": 1045, "cached_tokens": 784}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:32044398", "type": "paper", "label": "pmid:32044398"}, {"id": "source:pmid:32044398", "type": "manuscript", "label": "PMID 32044398 full text"}, {"id": "data:geo:GSE136153", "type": "dataset", "label": "GEO GSE136153"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:32044398", "type": "paper", "label": "pmid:32044398"}, {"id": "source:pmid:32044398", "type": "manuscript", "label": "PMID 32044398 full text"}, {"id": "data:geo:GSE136153", "type": "dataset", "label": "GEO GSE136153"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-32044398", "type": "extraction", "used": ["source:pmid:32044398"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE136153", "type": "accession_resolution", "used": ["data:geo:GSE136153"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:32044398", "parent_hash": "sha256:eca46504ca835c4119936dcd58bf0be1fc890641fb8de806b8daff7b9d4bdc3c", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE136153 licence not read", "asset:data:geo:GSE136153 not downloaded", "execution.not_run", "method", "operations", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["l-specific NCoR1-deficient mice (NCoR1ΔIEC). Mice were challenged with dextran sodium sulfate to in", "n. Colonic organoids cultured from NCoR1ΔIEC mice were more sensitive to butyrate-induced cell grow", "ore effective therapy. METHODS: We performed in vivo and in vitro studies from control (nuclear r", "Care and Use Committee. Both male and female mice were included, with siblings preferred for all th"], "order_basis": "paper_text_order:468", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["er permeability analysis, cell proliferation immunostaining assays, and RNA sequencing analysis. By usin"], "order_basis": "paper_text_order:803", "id": "assay:2"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ell proliferation immunostaining assays, and RNA sequencing analysis. By using crypt cultures, the organ", "e colonic crypt cells. Transcript profiling: RNA sequencing data have been deposited in the GEO database"], "order_basis": "paper_text_order:830", "id": "assay:3"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["noid-forming efficiency, cell proliferation, apoptosis, and histone acetylation were analyzed after", "butyrate-induced cell growth inhibition and apoptosis, which were exaggerated further by tumor nec"], "order_basis": "paper_text_order:933", "id": "assay:4"}]}