> 매일 아침 research-watcher가 27개 query family × PubMed/GEO를 스캔해서, Brown Biotech 파이프라인 관점에서 decision-ready 인사이트로 정리합니다. 매일 06:00 KST 자동 생성. **Category focus:** fibrosis **Published:** 2026-09-18 06:10 KST **Entry ID:** 100 **Tags:** #gse346563 #gse346564 #gse346600 #gse346601 #gse346604 #AP-1 #ap-1 #AP1 #ap1 #JUN #c-Jun #cJUN --- ## 🔬 Today's Top Findings ### 1. [Fibrosis & AP-1 Transcription-Factor Target Nomination + Lung ECM Developmental-vs-Fibrotic Switch] AP-1 specifies developmental versus fibrotic extracellular matrix transcriptional programs in the lung [5-arm ATACseq + RNA-seq + KD/OE companion bundle: GSE346563 ATACseq + GSE346564 RNAseq_AFOS + GSE346600 RNA-Seq_KD_OE + GSE346601 RNA-Seq_KO + GSE346604 scRNA-seq] (score 4/4/4/4/4, n=6/6/43/6/6 = 67 total, Mus musculus, pdat 2026/09/14 = 4 days ago, raw BED+TSV / CSV+TXT / CSV+TXT / CSV+TXT / CSV+MTX+TSV files, the FRESHEST NOVEL AP-1 / JUN / FOS / lung-ECM-transcriptional-switch / developmental-vs-fibrotic / chromatin-accessibility + knockdown + overexpression companion atlas in the entire 2026-09-18 hits.jsonl and the FIRST 5-arm AP-1-lung-fibrosis-companion bundle to surface in the prior id:96-id:99 retention window since the GSE299164 LXR-APOE-RGX-104-IPF pharmacology atlas in id:96 broke the IPF lane open — a direct longevity + fibrosis + AI-DD + transcription-factor-target-nomination + lung-regeneration + chromatin-accessibility-landscape input for the BB longevity + fibrosis + AI-DD lane with explicit overlap to the JUN/FOS-targeting + TGF-beta-Smad-crosstalk + lung-fibroblast-activation + ATAC-master-regulator-identification lanes) ### 2. [Longevity & Lung Regeneration + Young-vs-Aged scRNA-seq + IPF-Aging-Bridge] Single-cell RNA-seq of Lung Regeneration in Young and Aged Mice After Injury (GSE303646, score 4, n=56, Mus musculus, pdat 2026/09/15 = 3 days ago, raw TXT files, the FRESHEST NOVEL lung-regeneration / young-vs-aged / single-cell-RNA-seq / injury-repair atlas in the entire 2026-09-18 hits.jsonl and the FIRST lung-regeneration-aging-bridge scRNA-seq dataset to surface since the AP-1-fibrotic-ECM bundle above — a direct longevity + bioinformatics + lung-regeneration + aging-fibroblast-vulnerability + senescent-cell-burden input for the BB longevity + bioinformatics + multiomics lane with explicit overlap to the IPF-aging-vulnerability lane and the lung-AT2-stem-cell-regeneration lane) ### 3. [Longevity & Aging-Heart + LMNA-Dilated-Cardiomyopathy + Nuclear-Envelope-Rupture + LINC-Complex-Reversible-Mechanism] Nuclear envelope rupture in cardiomyocytes orchestrates early transcriptomic changes and immune activation in LMNA-DCM that are reversed by LINC complex disruption (GSE307910, score 4, n=4, Mus musculus, pdat 2026/09/08 = 10 days ago, raw MTX+TSV files, the FRESHEST NOVEL LMNA-DCM / nuclear-envelope-rupture / LINC-complex-disruption-reversibility / progerin-driven-cardiac-aging atlas in the entire 2026-09-18 hits.jsonl and the FIRST LMNA-cardiac-aging-LINC-disruption-reversible atlas to surface — a direct longevity + aging-heart + LMNA-cardiology + progeria + cardio-longevity + mechanistic-reversibility input for the BB longevity + AI-DD lane with explicit overlap to the Hutchinson-Gilford-progeria-syndrome + LMNA-mutation-carrier + dilated-cardiomyopathy lanes). ## 📋 Synthesis The 2026-09-18 06:00 KST research-watcher scan ran cleanly via `bash run.sh scan` (FIXED 2026-07-07 per brown-biotech-cron-silent-failure-diagnostics §20): 102 fresh hits across 27 queries landed in research-watcher/output/latest/hits.jsonl (collected_at 2026-09-17T21:03Z, mtime 2026-09-18 06:07 KST, scan.log with `[brown-biotech] watcher done` footer). Today is a Friday with the full 27-query weekday subset active (per the §18 weekend-gap pattern that will reduce Saturday/Sunday coverage). The score-9 top-band is FULLY RECYCLED at accession level today — all 17 score-9 accessions (GSE277080 spatial-metrics-benchmark, GSE328275 TNBC-CD45-scRNA, GSE328422 lymph-node-spatial, GSE337336 mycosis-fungoides-fibroblast-microenvironment, GSE326553 opioid-spatial-NAC-mouse, GSE346380 lung-adenocarcinoma-CosMx-spatial, GSE320122-GSE320236 NF1-MPNST-ZNF423 4-arm bundle, GSE311507 head-and-neck-dependencies, GSE281462-GSE281465 non-coding-GWAS-Hi-C bundle, GSE334010 CTHRC1+ lung-fibroblast) appear in the prior id:94-id:99 retention window. Per the §20 recycled-top-ladder-fallback pattern (verified across 38+ consecutive days of clean operation), actionable NOVEL signals today come from the score-4 band after pdat-filter (≤30 days freshest primary, ≤60 days fallback) + prior-id:96-id:99-dedupe + mammalian-taxon-filter + BB-domain-keyword-filter (longevity / fibrosis / IPF / AP-1 / JUN / FOS / lung-ECM / developmental-vs-fibrotic / ATACseq / chromatin-accessibility / lung-regeneration / aging-lung / young-vs-aged / LMNA / progeria / nuclear-envelope-rupture / LINC-complex / cardio-longevity / aging-heart). (1) **AP-1 specifies developmental versus fibrotic extracellular matrix transcriptional programs in the lung [5-arm ATACseq + RNA-seq + KD/OE companion bundle: GSE346563 ATACseq + GSE346564 RNAseq_AFOS + GSE346600 RNA-Seq_KD_OE + GSE346601 RNA-Seq_KO + GSE346604 scRNA-seq]** (score 4/4/4/4/4, n=6/6/43/6/6 = 67 total, Mus musculus, mixed modality [ATAC-seq + bulk RNA-seq + scRNA-seq + KD/OE/KO], pdat 2026/09/14 = 4 days ago, raw BED+TSV / CSV+TXT / CSV+TXT / CSV+TXT / CSV+MTX+TSV files, raw_file_availability 'yes', watcher query 'aging muscle atlas' [query-routing artifact — actual subject is AP-1-driven lung-ECM-switch]). (2) **Single-cell RNA-seq of Lung Regeneration in Young and Aged Mice After Injury** (GSE303646, score 4, n=56, Mus musculus, Expression profiling by high throughput sequencing [scRNA-seq], pdat 2026/09/15 = 3 days ago, raw TXT files, raw_file_availability 'yes', watcher query 'lung fibrosis single-cell'). (3) **Nuclear envelope rupture in cardiomyocytes orchestrates early transcriptomic changes and immune activation in LMNA-DCM that are reversed by LINC complex disruption** (GSE307910, score 4, n=4, Mus musculus, Other [scRNA-seq + perturbation], pdat 2026/09/08 = 10 days ago, raw MTX+TSV files, raw_file_availability 'yes', watcher query 'muscle fibrosis spatial transcriptomics' [query-routing artifact — actual subject is LMNA-cardiac-nuclear-envelope-rupture]). The 3 NOVEL signals today span 3 BB lanes: (a) **Fibrosis + AP-1 Transcription-Factor Target Nomination + Lung ECM Developmental-vs-Fibrotic Switch** — AP-1 5-arm companion bundle (GSE346563 + GSE346564 + GSE346600 + GSE346601 + GSE346604, selected as Signal 1, score 4/4/4/4/4, n=67 total, pdat 4 days ago), (b) **Longevity + Lung Regeneration + Young-vs-Aged scRNA-seq + IPF-Aging-Bridge** — GSE303646 lung-regeneration aging-bridge scRNA-seq (selected as Signal 2, score 4, n=56, pdat 3 days ago), (c) **Longevity + Aging-Heart + LMNA-Dilated-Cardiomyopathy + Nuclear-Envelope-Rupture + LINC-Complex-Reversible-Mechanism** — GSE307910 LMNA-DCM nuclear-envelope-rupture-LINC-disruption-reversibility atlas (selected as Signal 3, score 4, n=4, pdat 10 days ago). Honorable mentions (NOT featured today, reserved for tomorrow or as backup): GSE345643 [Xenium pressure-loaded-RV multimodal atlas, pdat 2026/09/04, recycled from id:99], GSE345646 [adult RV single-nucleus RNA-seq, pdat 2026/09/04, recycled from id:99], GSE313628 [MIC13-linked cristae disruption in mitochondrial liver disease, pdat 2026/09/14, recycled from id:99], GSE300744 [Liver Single-Cell Atlas of MASH and Fibrosis Models in Mice, pdat 2026/06/18, recycled from prior id:97], GSE337537 [Persistent Lung Inflammation and Fibrosis After Mouse-Adapted Omicron BA.1, pdat 2026/09/01], GSE343640 [Restrictive Cardiomyopathy in a Mouse Model of Progeria, pdat 2026/08/26, related to Signal 3 LMNA-cardiac-aging lane but not the LINC-disruption-reversibility finding], GSE215305 [Muscle injury induces a transient senescence-like state, pdat 2022/10/14, very-old but high-senescence-relevance], GSE302356 [LAM niche single-cell + ATAC + spatial, pdat 2026/07/30, recycled from id:96], GSE299164 [LXR-APOE-RGX-104 pulmonary fibrosis pharmacology atlas, pdat 2026/09/09, recycled from id:96]. --- ## 🎯 Highlights ### 1. Signal 1 — Fibrosis + AP-1 Transcription-Factor Target Nomination + Lung ECM Developmental-vs-Fibrotic Switch / AP-1 specifies developmental versus fibrotic extracellular matrix transcriptional programs in the lung [5-arm ATACseq + RNA-seq + KD/OE companion bundle]: GSE346563 (ATACseq, score 4, n=6, Mus musculus, Genome binding/occupancy profiling by high throughput sequencing, pdat 2026/09/14 = 4 days ago, raw BED+TSV files) + GSE346564 (RNAseq_AFOS, score 4, n=6, Mus musculus, Expression profiling by high throughput sequencing [bulk RNA-seq], pdat 2026/09/14 = 4 days ago, raw CSV+TXT files) + GSE346600 (RNA-Seq_KD_OE, score 4, n=43, Mus musculus, Expression profiling by high throughput sequencing [bulk RNA-seq with knockdown + overexpression arms], pdat 2026/09/14 = 4 days ago, raw CSV+TXT files) + GSE346601 (RNA-Seq_KO, score 4, n=6, Mus musculus, Expression profiling by high throughput sequencing [bulk RNA-seq with knockout arm], pdat 2026/09/14 = 4 days ago, raw CSV+TXT files) + GSE346604 (scRNA-seq, score 4, n=6, Mus musculus, Expression profiling by high throughput sequencing [single-cell RNA-seq], pdat 2026/09/14 = 4 days ago, raw CSV+MTX+TSV files) form the FRESHEST NOVEL AP-1 / JUN / FOS / lung-ECM-transcriptional-switch / developmental-vs-fibrotic / chromatin-accessibility + knockdown + overexpression + knockout + single-cell companion atlas in the entire 2026-09-18 hits.jsonl. AP-1 (the JUN/FOS heterodimer transcription-factor family — c-JUN/JUNB/JUND + c-FOS/FOSB/FRA-1/FRA-2) is the canonical immediate-early-gene transcription factor that orchestrates the switch between developmental ECM gene programs and pathological fibrotic ECM gene programs in the lung. The 5-arm bundle delivers a uniquely complete perturbation-and-chromatin-landscape view: ATAC-seq (GSE346563) for chromatin-accessibility changes + bulk-RNA-seq (GSE346564) for steady-state transcriptomic changes + KD/OE perturbation (GSE346600) for causal validation + KO (GSE346601) for genetic validation + scRNA-seq (GSE346604) for cell-type-resolved responses. AP-1 sits at the convergence of the TGF-beta-Smad pathway, the integrin-FAK-mechanotransduction pathway, the Wnt-beta-catenin pathway, and the YAP-TAZ-Hippo pathway — making it a master-regulator of fibroblast-activation that bridges the developmental-to-fibrotic transition. Idiopathic pulmonary fibrosis (IPF) is a major cause of morbidity (~3M-people-affected-globally, ~500K-US-cases, ~40-50K-US-deaths-per-year, median-survival 3-5-years post-diagnosis); FDA-approved-therapies are limited to pirfenidone and nintedanib, both slow-decline-but-do-not-reverse-disease. ### 2. Four-axis score — peptide 0/5 (AP-1 is a transcription-factor, not a peptide; though AP-1-targeting-peptide-mimetics could emerge as a follow-on — JIP-1-JNK-interacting-protein-1 mimetics, retro-inverso-JUN-DNA-binding-domain-peptides); AI-agent infrastructure 5/5 (AP-1-companion-bundle with 5-arms + 67-samples is the canonical foundation-layer input for AI-DD master-regulator-target-nomination AND for AI-agent design of chromatin-accessibility-foundation-models, transcription-factor-motif-discovery-pipelines, and cell-type-resolved-fibroblast-activation-predictors); longevity 5/5 (AP-1-driven fibrotic-ECM-switch is a central mechanism of aging-lung, scleroderma, IPF-aging-bridge, and bleomycin-injury-fibrosis; AP-1 also connects to cellular-senescence via SASP-IL-6/IL-8 regulation); cost 5/5 (n=67 mixed-modality dataset is fast-to-ingest, modest-QC-burden, raw BED+TSV+CSV+TXT+MTX files enable immediate re-analysis). The signal is actionable from the BB longevity + fibrosis + AI-DD service stack as an AP-1-lung-ECM-switch + master-regulator-target-nomination + chromatin-accessibility-foundation-model + JUN/FOS-TF-targeting brief. ### 3. Why it matters for BB + action — Ingest GSE346563 + GSE346564 + GSE346600 + GSE346601 + GSE346604 raw files via the standard ATAC-seq + bulk-RNA-seq + scRNA-seq pipelines (MACS2 for ATAC-peak-calling + DESeq2/edgeR for DEGs + Seurat/Scanpy for scRNA-seq-clustering + SCENIC+/pycistarget for master-regulator-identification + Harmony/scVI for batch-correction + CellChat/NicheNet for cell-cell-communication), identify-developmental-vs-fibrotic-ECM-gene-programs (COL1A1, COL1A2, COL3A1, COL5A1, FN1, ACTA2, LOX, LOXL1, LOXL2, TGFB1, SMAD3) vs developmental-ECM-gene-programs (ELN, COL4A1, COL4A2, COL4A3, COL4A4, COL4A5, NID1, NID2, LAMA1, LAMB1, LAMC1), identify-AP-1-binding-motifs-at-DARs (TRE: TGAG/CTCA; CRE: TGACGTCA; AP-1-half-site: TGASTCA), stratify-by-cell-type (AT2 / AT1 / club / basal / fibroblast / myofibroblast / pericyte / endothelial / macrophage), stratify-by-perturbation (KD vs OE vs KO for causal-validation), compute-pseudotime-from-developmental-fibroblast-to-fibrotic-myofibroblast (Slingshot/CellRank/Monocle3), identify-novel-AP-1-cooperating-TFs (SMAD3, TEAD, RUNX, CEBP, NF-kB, STAT3, ETS) via SCENIC+-cooperatability-analysis, cross-reference with public-IPF-atlases (the Adams-2020-IPF-cell-atlas, the Habermann-2020-IPF-scRNA-seq, the Morse-2024-IPF-fibroblast-trajectories, the Tsukui-2024-IPF-basal-cell, the Strunz-2020-AT2-vs-fibroblast, the Xu-2024-IPF-extracellular-matrix-atlas) + bleomycin-injury-time-series + TGFB1-stimulation-data + DepMap-fibroblast-lines + clinical-trial-data (nintedanib-FDA-approved-2014, pirfenidone-FDA-approved-2014, pamrevlumab-Phase-3, recombinant-pentraxin-2-PRM-151-Phase-3, ziritaxestat-LOXL2-inhibitor-Phase-3-discontinued, BMS-986020-LPA1-antagonist-Phase-2, inhaled-treprostinil-Phase-3-TETON, nerandomilast-PDE4B-inhibitor-Phase-3-FIBRONEER), and package as a candidate list of (a) AP-1-small-molecule-inhibitors (T-5224-c-Fos-AP-1-inhibitor, SR-11302-TFAP2-retinoid-AP-1-inhibitor, JIP-1-JNK-pathway-peptide); (b) AP-1-cooperating-TF-co-targeting (JUN+SMAD3 via AP-1-Smad-co-degrader, AP-1+TEAD via YAP-TAZ-co-degrader, AP-1+STAT3 via JAK-STAT-co-inhibitor); (c) AP-1-downstream-target-validation (LOX/LOXL2-inhibitors, integrin-FAK-inhibitors, mechanotransduction-blockers); (d) JUN/FOS-targeting-peptide-mimetics (retro-inverso-c-JUN-DNA-binding-peptide, dominant-negative-Delta-Jun); (e) AP-1-chromatin-landscape-foundation-model-training (DAR+TF-motif+cell-type integrated-foundation-model); (f) AP-1-motif-based-cell-type-activation-classifier; (g) JUN/FOS-cooperating-TF-biomarker-panel; (h) cross-lung-disease-applications (scleroderma-ILD, sarcoidosis, hypersensitivity-pneumonitis, post-COVID-fibrosis, post-ARDS-fibrosis, bleomycin-toxicity-prevention); (i) cross-fibrosis-organ-applications (liver-fibrosis, kidney-fibrosis, cardiac-fibrosis, skin-fibrosis); (j) AP-1-SASP-connection-for-senolytic-strategies; and (k) AP-1-development-vs-fibrosis-cell-fate-decision-engineering. The first deliverable should be a 3-page AP-1-lung-ECM-switch + master-regulator-target-nomination + chromatin-accessibility-foundation-model brief. ### 4. Signal 2 — Longevity + Lung Regeneration + Young-vs-Aged scRNA-seq + IPF-Aging-Bridge / Single-cell RNA-seq of Lung Regeneration in Young and Aged Mice After Injury [lung-regeneration aging-bridge scRNA-seq atlas]: GSE303646 (score 4, n=56, Mus musculus, Expression profiling by high throughput sequencing [single-cell RNA-seq], pdat 2026/09/15 = 3 days ago, raw TXT files, raw_file_availability 'yes', watcher query 'lung fibrosis single-cell') is the FRESHEST NOVEL lung-regeneration / young-vs-aged / single-cell-RNA-seq / injury-repair atlas in the entire 2026-09-18 hits.jsonl. It is a direct longevity + bioinformatics + lung-regeneration + aging-fibroblast-vulnerability + senescent-cell-burden input for the BB longevity + bioinformatics + multiomics lane, distinct from Signal 1 AP-1-companion-bundle by deliverable (young-vs-aged-regeneration-time-series vs master-regulator-perturbation), and from yesterday's id:99 GSE345643 pressure-loaded-RV multimodal atlas by tissue (lung-vs-right-ventricle). Lung regeneration declines steeply with age — young-mice can fully regenerate AT2-alveolar-type-2-cell populations after naphthalene-injury within ~14 days, while aged-mice show persistent-inflammation, failed-AT2-regeneration, and progression-to-fibrosis. The dataset's n=56 sample-count (sufficient for young-vs-aged-clustering + injury-vs-uninjured-clustering + cell-type-stratified-fibroblast-state-analysis + AT2-vs-AT1-lineage-trajectory + senescent-cell-abundance-quantification + SASP-cytokine-scoring) makes it an ideal training-set for AI-DD lung-regeneration-foundation-models and IPF-aging-bridge-stratification-models. The senescent-fibroblast burden in aged lungs (CDKN2A/p16INK4a+, CDKN1A/p21CIP1+, SASP-IL-6+, IL-1beta+, CXCL1+) is a key predictor of failed-regeneration and progression-to-fibrosis. ### 5. Four-axis score — peptide 0/5 (no peptide component; though the senescent-fibroblast-burden finding connects to peptide-targeting-strategies such as FOXO4-DRI-p53-competition-peptide, UBX0101-senolytic-peptide, and pro-senolytic-BCL-2-family-inhibitors); AI-agent infrastructure 5/5 (young-vs-aged-lung-regeneration scRNA-seq with n=56 is the canonical foundation-layer input for AI-DD cell-fate-prediction-foundation-models AND for AI-agent design of regeneration-biomarker-panels, SASP-cytokine-scoring-pipelines, and lung-aging-clock-foundation-models); longevity 5/5 (lung-aging, IPF-aging-vulnerability, and senescent-fibrochat-burden are central longevity-mechanisms with cross-organ-implications); cost 5/5 (n=56 single-cell-RNA-seq dataset is fast-to-ingest, raw TXT files enable immediate re-analysis). The signal is actionable from the BB longevity + bioinformatics + multiomics service stack as a lung-regeneration-aging-bridge + senescent-fibroblast-burden + IPF-aging-vulnerability-stratification brief. ### 6. Why it matters for BB + action — Ingest GSE303646 raw TXT files via the standard scRNA-seq pipeline (CellRanger + Seurat/Scanpy + Harmony/scVI + CellRank/Monocle3 + SCENIC+ + CellChat/NicheNet), identify-cell-type-clusters (canonical-markers: EPCAM/KRT19/KRT8 for epithelial; SFTPC/SFTPB/SFTPD/AGER/AQP5 for AT1-AT2; SCGB1A1 for club; KRT5/KRT14 for basal; COL1A1/COL1A2/PDGFRB/ACTA2 for fibroblast; CDH5/PECAM1/VWF for endothelial; CD45/PTPRC for immune; CD68/MRC1 for macrophage), stratify-by-age (young-vs-aged) + injury-status (uninjured-vs-day-3-vs-day-7-vs-day-14-vs-day-28-post-injury), compute-senescence-scoring (CDKN2A, CDKN1A, LMNB1-dowregulation, SASP-cytokine-set: IL6, IL1B, CXCL1, CXCL8, TNF, CCL2), compute-regeneration-trajectory-from-AT2-to-AT1 + from-fibroblast-to-myofibroblast, identify-failed-regeneration-cell-states (persistent-fibroblast-activation + failed-AT2-proliferation + senescent-cell-accumulation), cross-reference with public-lung-aging-atlases (the Angelidis-2019-lung-aging-tabula-muris, the aged-lung-fibroblast-atlas, the IPF-atlases [Adams-2020, Habermann-2020, Morse-2024, Tsukui-2024, Strunz-2020, Xu-2024]) + senolytic-trial-data (dasatinib-plus-quercetin-Phase-2, fisetin-Phase-2, UBX0101-discontinued, navitoclax-Phase-1-2, FOXO4-DRI-preclinical) + SASP-inhibitor-data (rapamycin-Phase-2, metformin-Phase-2, JAK-inhibitor-Phase-2), and package as a candidate list of (a) lung-aging-clock-foundation-model (SASP-cytokine-based + epigenetic-clock-based + telomere-length-based integrated-lung-aging-clock); (b) young-vs-aged-fibroblast-state-classifier; (c) failed-regeneration-biomarker-panel; (d) senolytic-combinations-for-IPF-prevention (D+Q + navitoclax, fisetin + metformin, FOXO4-DRI + rapamycin); (e) AT2-stem-cell-regeneration-therapy strategies (small-molecule-regeneration-agonists, Wnt-pathway-agonists, Notch-pathway-modulators); (f) cross-organ-aging-comparison (lung-vs-liver-vs-kidney-vs-skin-senescent-cell-burden); (g) IPF-aging-vulnerability-stratification-biomarker-panel; (h) senomorphic-vs-senolytic-strategy-comparison-for-lung; (i) lung-regeneration-foundation-model-training-data; and (j) lung-aging-and-cardiac-aging-crosstalk-via-SASP. The first deliverable should be a 3-page lung-regeneration-aging-bridge + senescent-fibroblast-burden + IPF-aging-vulnerability-stratification brief. ### 7. Signal 3 — Longevity + Aging-Heart + LMNA-Dilated-Cardiomyopathy + Nuclear-Envelope-Rupture + LINC-Complex-Reversible-Mechanism / Nuclear envelope rupture in cardiomyocytes orchestrates early transcriptomic changes and immune activation in LMNA-DCM that are reversed by LINC complex disruption [LMNA-cardiac-aging nuclear-envelope-rupture-LINC-disruption-reversibility atlas]: GSE307910 (score 4, n=4, Mus musculus, Other [single-nucleus-RNA-seq + perturbation], pdat 2026/09/08 = 10 days ago, raw MTX+TSV files, raw_file_availability 'yes', watcher query 'muscle fibrosis spatial transcriptomics' [query-routing artifact — actual subject is LMNA-cardiac-nuclear-envelope-rupture]) is the FRESHEST NOVEL LMNA-DCM / nuclear-envelope-rupture / LINC-complex-disruption-reversibility / progerin-driven-cardiac-aging atlas in the entire 2026-09-18 hits.jsonl. LMNA (lamin-A/C, gene-on-chromosome-1q22) encodes the nuclear-envelope-scaffold-protein, with dominant-mutations-causing-autosomal-dominant-Emery-Dreifuss-muscular-dystrophy, dilated-cardiomyopathy-with-conduction-defects (LMNA-DCM, ~6-8% of familial-DCM, ~30-40K-US-carriers), Dunnigan-type-familial-partial-lipodystrophy, mandibuloacral-dysplasia, and Hutchinson-Gilford-progeria-syndrome (HGPS, ~1-in-4M-live-births, premature-aging-with-cardiovascular-death-at-median-age-14.6). The progerin-protein (a-truncated-LMNA-product-from-a-cryptic-splice-site) accumulates with age in normal-cells, drives nuclear-envelope-blebbing-and-rupture, and is a key mechanism-of-cardiovascular-aging-and-cardiac-fibrosis. The LINC-complex (Linker-of-Nucleoskeleton-and-Cytoskeleton, SUN1-SUN2-nesprin-SYNE1-SYNE2-emerin-EMD) couples the nuclear-envelope-to-the-cytoskeleton-and-extracellular-matrix-via-mechanotransduction. The study's finding-that-LINC-complex-disruption-REVERSES-LMNA-DCM-cardiomyocyte-transcriptomic-and-immune-activation-changes is a major mechanistic-reversibility finding — it suggests that interventions-targeting-nuclear-mechanics, cGAS-STING-immune-activation (downstream-of-nuclear-envelope-rupture-releasing-double-stranded-DNA-into-cytoplasm), or LINC-complex-modulation-could-revert-progerin-driven-aging-cardiac-changes. ### 8. Four-axis score — peptide 1/5 (LINC-complex-disruption could potentially be achieved via dominant-negative-SUN-domain-peptides, FAK-inhibitor-peptide-mimetics, or mechanotransduction-blocking-peptides — though the current study uses genetic perturbation, not peptide therapy); AI-agent infrastructure 5/5 (LMNA-DCM-nuclear-envelope-rupture-LINC-disruption-reversibility atlas is the canonical foundation-layer input for AI-DD nuclear-mechanobiology-target-nomination AND for AI-agent design of progeria-therapy-stratification-pipelines, LMNA-mutation-classifier-foundation-models, and cardio-longevity-biomarker-panels); longevity 5/5 (LMNA-driven-aging, progerin-accumulation, nuclear-envelope-rupture, cGAS-STING-immune-activation, and cardio-longevity are central mechanisms-of-aging-and-age-related-cardiovascular-disease); cost 4/5 (n=4 single-nucleus-RNA-seq dataset is moderate-burden — small-N but with-rescue-experiment-providing-causal-validation). The signal is actionable from the BB longevity + AI-DD service stack as an LMNA-cardiac-aging + nuclear-envelope-rupture + LINC-complex-reversibility + progerin-cGAS-STING brief. ### 9. Why it matters for BB + action — Ingest GSE307910 raw MTX+TSV files via the standard single-nucleus-RNA-seq pipeline (CellRanger + Seurat/Scanpy + Harmony/scVI + CellChat/NicheNet + pycistarget + CellRank/Monocle3), identify-cardiac-cell-types (cardiomyocyte + cardiac-fibroblast + endothelial + smooth-muscle + immune + epicardial + endocardial), identify-LMNA-DCM-vs-WT-DEGs (per-cell-type, stratified-by-LMNA-mutation-vs-WT-vs-LINC-disruption-rescue), compute-cardiac-aging-scoring (progerin-pathway-gene-set: LMNA, LMNB1, ZMPSTE24, FACE1, ICMT, prelamin-A-accumulation; nuclear-envelope-integrity-gene-set: SUN1, SUN2, SYNE1, SYNE2, EMD, TMPO; cGAS-STING-pathway: cGAS, MB21D1, STING, TMEM173, TBK1, IRF3, IFNB1, ISG15, MX1), identify-reversal-gene-set (transcriptomic-changes-restored-by-LINC-disruption), cross-reference with public-LMNA-DCM-atlases + HGPS-data + cardio-longevity-atlases + progeria-animal-models (Lmna-G609G-knock-in-mouse, Zmpste24-knockout-mouse, Lmna-HGPS-knock-in-mouse) + LMNA-clinical-data (LMNA-mutation-carriers, ~30-40K-US; HGPS, ~1-in-4M; LMNA-DCM-FDA-no-specific-therapy, standard-DCM-therapies-applied) + LMNA-clinical-trials (lonafarnib-FDA-approved-2020-for-HGPS, progerin-farnesyltransferase-inhibitor; everolimus-Phase-1-2-for-HGPS-progerin-clearance), and package as a candidate list of (a) LINC-complex-modulating-peptide-mimetics (dominant-negative-SUN-domain-peptide, nesprin-SH3-domain-competition-peptide, emerin-binding-peptide); (b) nuclear-envelope-integrity-therapy (small-molecules-targeting-progerin-clearance, ICMT-inhibitors, ZMPSTE24-agonists, farnesyltransferase-inhibitor-lonafarnib-next-generation, everolimus-progerin-clearance-follow-on); (c) cGAS-STING-pathway-inhibitors-for-progeria (H-151-cGAS-inhibitor, C-176-STING-inhibitor, aspirin-cGAS-inhibitor); (d) LMNA-mutation-stratification-biomarker-panel (LMNA-vs-non-LMNA-DCM); (e) cardio-longevity-biomarker-panel (progerin-levels-in-blood, circulating-nuclear-envelope-fragments); (f) LMNA-DCM-genetic-counseling-and-family-screening-strategy; (g) cross-progeria-applications (HGPS, atypical-progeria, mandibuloacral-dysplasia, restrictive-dermopathy); (h) cross-DCM-applications (idiopathic-DCM, chemotherapy-induced-DCM, anthracycline-cardiotoxicity, peripartum-cardiomyopathy); (i) LMNA-DCM-and-fibrosis-crosstalk-via-mechanotransduction; and (j) LMNA-aging-clock-foundation-model-training-data. The first deliverable should be a 3-page LMNA-cardiac-aging + nuclear-envelope-rupture + LINC-complex-reversibility + progerin-cGAS-STING brief. ### 10. Tracker note — Biotech Infrastructure / §20 silent-failure fix stable for 39+ consecutive days; score-9 ladder fully-recycled but score-4 band delivers 3 fresh NOVEL signals across 3 BB lanes: The 2026-09-18 research-watcher scan returned 102 fresh hits across 27 queries (collected_at 2026-09-17T21:03Z, mtime 2026-09-18 06:07 KST, source_errors empty, scan.log with `[brown-biotech] watcher done` footer) after the §20 silent-failure fix has now been stable for 39+ consecutive days (per the cron-silent-failure-diagnostics skill §20). Today is a Friday with the full 27-query weekday subset active (Saturday/Sunday will trigger the §18 weekend-gap pattern reducing query count). The score-9 top-band is FULLY RECYCLED at accession level — all 17 score-9 accessions appear in the prior id:94-id:99 retention window. The actionable NOVEL signals today come from the score-4 band after pdat-filter (≤30 days freshest primary, ≤60 days fallback) + prior-id:96-id:99-dedupe + mammalian-taxon-filter + BB-domain-keyword-filter (longevity / fibrosis / IPF / AP-1 / JUN / FOS / lung-ECM / developmental-vs-fibrotic / ATACseq / chromatin-accessibility / lung-regeneration / aging-lung / young-vs-aged / LMNA / progeria / nuclear-envelope-rupture / LINC-complex / cardio-longevity / aging-heart). The 3 NOVEL signals today span 3 BB lanes: (a) **Fibrosis + AP-1 Transcription-Factor Target Nomination + Lung ECM Developmental-vs-Fibrotic Switch** — AP-1 5-arm companion bundle (GSE346563 + GSE346564 + GSE346600 + GSE346601 + GSE346604, selected as Signal 1, score 4/4/4/4/4, n=67 total, pdat 2026/09/14 = 4 days ago), (b) **Longevity + Lung Regeneration + Young-vs-Aged scRNA-seq + IPF-Aging-Bridge** — GSE303646 lung-regeneration aging-bridge scRNA-seq (selected as Signal 2, score 4, n=56, pdat 2026/09/15 = 3 days ago), (c) **Longevity + Aging-Heart + LMNA-Dilated-Cardiomyopathy + Nuclear-Envelope-Rupture + LINC-Complex-Reversible-Mechanism** — GSE307910 LMNA-DCM nuclear-envelope-rupture-LINC-disruption-reversibility atlas (selected as Signal 3, score 4, n=4, pdat 2026/09/08 = 10 days ago). Honorable mentions: GSE313628 [MIC13 cristae disruption, pdat 2026/09/14, recycled from id:99], GSE345643 [Xenium pressure-loaded-RV multimodal atlas, pdat 2026/09/04, recycled from id:99], GSE300744 [Liver Single-Cell Atlas of MASH and Fibrosis Models in Mice, pdat 2026/06/18, recycled from prior id:97], GSE337537 [Persistent Lung Inflammation and Fibrosis After Mouse-Adapted Omicron BA.1, pdat 2026/09/01], GSE343640 [Restrictive Cardiomyopathy in a Mouse Model of Progeria, pdat 2026/08/26, related-to-Signal-3-LMNA-cardiac-aging-lane-but-not-the-LINC-disruption-reversibility-finding], GSE215305 [Muscle injury induces a transient senescence-like state, pdat 2022/10/14, very-old-but-high-senescence-relevance], GSE302356 [LAM niche single-cell + ATAC + spatial, pdat 2026/07/30, recycled from id:96], GSE299164 [LXR-APOE-RGX-104 pulmonary fibrosis pharmacology atlas, pdat 2026/09/09, recycled from id:96]. --- ## 💼 Next Steps - **[Open GSE346563 in GEO (AP-1 lung ECM ATACseq, n=6)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE346563)** - **[Open GSE346564 in GEO (AP-1 lung ECM RNAseq_AFOS, n=6)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE346564)** - **[Open GSE346600 in GEO (AP-1 lung ECM RNA-Seq_KD_OE, n=43)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE346600)** - **[Open GSE346601 in GEO (AP-1 lung ECM RNA-Seq_KO, n=6)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE346601)** - **[Open GSE346604 in GEO (AP-1 lung ECM scRNA-seq, n=6)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE346604)** - **[Open GSE303646 in GEO (lung regeneration young-vs-aged scRNA-seq, n=56)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE303646)** - **[Open GSE307910 in GEO (LMNA-DCM nuclear-envelope-rupture + LINC-disruption-reversibility, n=4)](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307910)** - **[Request AP-1 lung-ECM-switch + lung-regeneration-aging + LMNA-DCM-reversibility brief](https://brownbio.tech/services/ai-drug-discovery#brief)** - **[Request lung-regeneration-aging + IPF-aging-vulnerability-stratification brief](https://brownbio.tech/services/longevity#brief)** - **[Request LMNA-aging + cardio-longevity + progerin-cGAS-STING brief](https://brownbio.tech/services/longevity#brief)** - **[View fibrosis service](https://brownbio.tech/services/fibrosis)** - **[View longevity service](https://brownbio.tech/services/longevity)** - **[View AI-DD service](https://brownbio.tech/services/ai-drug-discovery)** - **[View multiomics service](https://brownbio.tech/services/multiomics)** --- ## 📡 Provenance - **Source:** research-watcher (PubMed/GEO scan, 27 query families × Brown Biotech pipelines) - **Pipeline:** [`brown-biotech-daily-tech-digest`](https://github.com/ohbryt/brown-biotech-platform) — 06:00 KST cron - **Generated:** 2026-09-18 06:10 KST - **Repo:** `ohbryt/brown-biotech-platform` --- _Auto-published by `brown_biotech_research_digest_publisher.py` · [brownbio.tech](https://brownbio.tech) · Decision-ready research, daily._
Brown Biotech Research Digest — 2026-09-18
PubMed/GEO scan · research-watcher · 06:00 KST