Temporal dynamics of the developing lung transcriptome in three common inbred strains of laboratory mice reveals multiple stages of postnatal alveolar development.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:27602285", "kind": "science-record", "revision": 7, "content_hash": "sha256:b5764561863e768062a9650dbb2a1b03e3cd554f6918cfb21119ce26618f30c4", "created_at": "2026-11-01T15:40:20Z", "updated_at": "2026-11-01T21:59:08Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Temporal dynamics of the developing lung transcriptome in three common inbred strains of laboratory mice reveals multiple stages of postnatal alveolar development.", "doi": "10.7717/peerj.2318", "pmid": "27602285", "authors": ["Kyle J Beauchemin", "Julie M Wells", "Alvin T Kho", "Vivek M Philip", "Daniela Kamir", "Isaac S Kohane", "Joel H Graber", "Carol J Bult"], "journal": "PeerJ", "year": 2016, "abstract": "To characterize temporal patterns of transcriptional activity during normal lung development, we generated genome wide gene expression data for 26 pre- and post-natal time points in three common inbred strains of laboratory mice (C57BL/6J, A/J, and C3H/HeJ). Using Principal Component Analysis and least squares regression modeling, we identified both strain-independent and strain-dependent patterns of gene expression. The 4,683 genes contributing to the strain-independent expression patterns were used to define a murine Developing Lung Characteristic Subtranscriptome (mDLCS). Regression modeling of the Principal Components supported the four canonical stages of mammalian embryonic lung development (embryonic, pseudoglandular, canalicular, saccular) defined previously by morphology and histology. For postnatal alveolar development, the regression model was consistent with four stages of alveolarization characterized by episodic transcriptional activity of genes related to pulmonary vascularization. Genes expressed in a strain-dependent manner were enriched for annotations related to neurogenesis, extracellular matrix organization, and Wnt signaling. Finally, a comparison of mouse and human transcriptomics from pre-natal stages of lung development revealed conservation of pathways associated with cell cycle, axon guidance, immune function, and metabolism as well as organism-specific expression of genes associated with extracellular matrix organization and protein modification. The mouse lung development transcriptome data generated for this study serves as a unique reference set to identify genes and pathways essential for normal mammalian lung development and for investigations into the developmental origins of respiratory disease and cancer. The gene expression data are available from the Gene Expression Omnibus (GEO) archive (GSE74243). Temporal expression patterns of mouse genes can be investigated using a study specific web resource (http://lungdevelopment.jax.org).", "claims": [{"id": "claim-method", "statement": "Using Principal Component Analysis and least squares regression modeling, we identified both strain-independent and strain-dependent patterns of gene expression.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:27602285", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Using Principal Component Analysis and least squares regression modeling, we identified both strain-independent and strain-dependent patterns of gene expression."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw data has been supplied as Supplemental files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:27602285", "locator": "sections[34] \"Data Availability\" paragraph 2", "quote": "The raw data has been supplied as Supplemental files."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study used Principal Component Analysis and least squares regression modeling to identify strain-independent and strain-dependent gene-expression patterns; the 4,683 genes contributing to strain-independent patterns defined the murine Developing Lung Characteristic Subtranscriptome (mDLCS). The raw and processed source data are available through GEO accession GSE74243.", "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:27602285"], "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:GSE74243"], "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:GSE74243"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:27602285", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.2318", "sha256": "sha256:036bb703b51643d7c44c0daf0edf6daf87da7af56c35154a2de1168cceab722a", "bytes": 109950, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.7717/peerj.2318", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC4991849", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE74243", "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=GSE74243", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE74243", "version": null, "note": "The raw data has been supplied as Supplemental files.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The raw data has been supplied as Supplemental files.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1915262", "GSM1915263", "GSM1915264", "GSM1915265", "GSM1915266", "GSM1915267", "GSM1915268", "GSM1915269", "GSM1915270", "GSM1915271", "GSM1915272", "GSM1915273", "GSM1915274", "GSM1915275", "GSM1915276", "GSM1915277", "GSM1915278", "GSM1915279", "GSM1915280", "GSM1915281", "GSM1915282", "GSM1915283", "GSM1915284", "GSM1915285", "GSM1915286", "GSM1915287", "GSM1915288", "GSM1915289", "GSM1915290", "GSM1915291", "GSM1915292", "GSM1915293", "GSM1915294", "GSM1915295", "GSM1915296", "GSM1915297", "GSM1915298", "GSM1915299", "GSM1915300", "GSM1915301", "GSM1915302", "GSM1915303", "GSM1915304", "GSM1915305", "GSM1915306", "GSM1915307", "GSM1915308", "GSM1915309", "GSM1915310", "GSM1915311", "GSM1915312", "GSM1915313", "GSM1915314", "GSM1915315", "GSM1915316", "GSM1915317", "GSM1915318", "GSM1915319", "GSM1915320", "GSM1915321", "GSM1915322", "GSM1915323", "GSM1915324", "GSM1915325", "GSM1915326", "GSM1915327", "GSM1915328", "GSM1915329", "GSM1915330", "GSM1915331", "GSM1915332", "GSM1915333", "GSM1915334", "GSM1915335", "GSM1915336", "GSM1915337", "GSM1915338", "GSM1915339", "GSM1915340", "GSM1915341", "GSM1915342", "GSM1915343", "GSM1915344", "GSM1915345", "GSM1915346", "GSM1915347", "GSM1915348", "GSM1915349", "GSM1915350", "GSM1915351", "GSM1915352", "GSM1915353", "GSM1915354", "GSM1915355", "GSM1915356", "GSM1915357", "GSM1915358", "GSM1915359", "GSM1915360", "GSM1915361", "GSM1915362", "GSM1915363", "GSM1915364", "GSM1915365", "GSM1915366", "GSM1915367", "GSM1915368", "GSM1915369", "GSM1915370", "GSM1915371", "GSM1915372", "GSM1915373", "GSM1915374", "GSM1915375", "GSM1915376", "GSM1915377", "GSM1915378", "GSM1915379", "GSM1915380", "GSM1915381", "GSM1915382", "GSM1915383", "GSM1915384", "GSM1915385", "GSM1915386", "GSM1915387", "GSM1915388", "GSM1915389", "GSM1915390", "GSM1915391", "GSM1915392", "GSM1915393", "GSM1915394", "GSM1915395", "GSM1915396", "GSM1915397", "GSM1915398", "GSM1915399", "GSM1915400", "GSM1915401", "GSM1915402", "GSM1915403", "GSM1915404", "GSM1915405", "GSM1915406", "GSM1915407", "GSM1915408", "GSM1915409", "GSM1915410", "GSM1915411", "GSM1915412", "GSM1915413", "GSM1915414", "GSM1915415", "GSM1915416", "GSM1915417", "GSM1915418", "GSM1915419", "GSM1915420", "GSM1915421", "GSM1915422", "GSM1915423", "GSM1915424", "GSM1915425", "GSM1915426", "GSM1915427", "GSM1915428", "GSM1915429", "GSM1915430", "GSM1915431", "GSM1915432", "GSM1915433", "GSM1915434", "GSM1915435", "GSM1915436", "GSM1915437", "GSM1915438", "GSM1915439", "GSM1915440", "GSM1915441", "GSM1915442", "GSM1915443", "GSM1915444", "GSM1915445", "GSM1915446", "GSM1915447", "GSM1915448", "GSM1915449", "GSM1915450", "GSM1915451", "GSM1915452", "GSM1915453", "GSM1915454", "GSM1915455", "GSM1915456", "GSM1915457", "GSM1915458", "GSM1915459", "GSM1915460", "GSM1915461", "GSM1915462", "GSM1915463", "GSM1915464", "GSM1915465", "GSM1915466", "GSM1915467", "GSM1915468", "GSM1915469", "GSM1915470", "GSM1915471", "GSM1915472", "GSM1915473", "GSM1915474", "GSM1915475", "GSM1915476", "GSM1915477"], "sample_count": 216, "group_sizes": null, "group_sizes_basis": null, "platform": "20894", "taxon": "Mus musculus", "title": "Genome wide gene expression during lung development in three inbred mouse strains", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:27602285:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:0bb17b89ec9b2631504628bb953a3630ea50b4de6e6f1efff24b5250b7e9f76a", "bytes": 2740, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[6]/table-wrap[1]#table-1", "version": null, "note": "Summary of analysis results for lung development transcriptional profiling in three inbred mouse strainse.The cumulative variation in gene expression accounted for by the first 10 principal components is 80.9%. Pearson Correlation results are from the pairwise correlation of PCA scores as a function of strain. Regression results show the significance levels of the effect of three variables (developmental stage, strain, and stage by strain interaction) for each Principal Component. Tukey HSD connecting letters diagram indicates relatedness of strains for each component.", "structure": {"pmcid": "PMC4991849", "section_index": 6, "section_title": "Regression analysis", "row_count": 31, "column_count": 8}, "table": {"label": "Table 1", "caption": "Summary of analysis results for lung development transcriptional profiling in three inbred mouse strainse.The cumulative variation in gene expression accounted for by the first 10 principal components is 80.9%. Pearson Correlation results are from the pairwise correlation of PCA scores as a function of strain. Regression results show the significance levels of the effect of three variables (developmental stage, strain, and stage by strain interaction) for each Principal Component. Tukey HSD connecting letters diagram indicates relatedness of strains for each component.", "rows": [["Component", "Var. (%)", "Pearson Correlation (R2)", "Regression (Pval)", "Tukey HSD"], ["PC1", "55.1 (55.1)", "C57BL/6J-A/J", ".990***", "Stage", "<.0001†", "AJ", "A"], ["A/J-C3H/HeJ", ".993***", "Strain", "0.9131", "B6", "A"], ["C57BL/6J-C3H/HeJ", ".990***", "Stage*strain", "0.6566", "C3H", "A"], ["PC2", "6.1 (61.2)", "C57BL/6J-A/J", ".744***", "Stage", "<.0001†", "AJ", "A"], ["A/J-C3H/HeJ", ".839***", "Strain", "0.5970", "B6", "A"], ["C57BL/6J-C3H/HeJ", ".849***", "Stage*strain", "0.0038", "C3H", "A"], ["PC3", "4.98 (66.2)", "C57BL/6J-A/J", ".865***", "Stage", "<.0001†", "AJ", "A"], ["A/J-C3H/HeJ", ".739***", "Strain", "0.2229", "B6", "A"], ["C57BL/6J-C3H/HeJ", ".646***", "Stage*strain", "0.2090", "C3H", "A"], ["PC4", "3.53 (69.7)", "C57BL/6J-A/J", ".117", "Stage", "<.0001†", "AJ", "B"], ["A/J-C3H/HeJ", ".114", "Strain", "0.0072", "B6", "B"], ["C57BL/6J-C3H/HeJ", ".192", "Stage*strain", "0.0029", "C3H", "A"], ["PC5", "2.83 (72.5)", "C57BL/6J-A/J", ".379*", "Stage", "<.0001†", "AJ", "B"], ["A/J-C3H/HeJ", ".445**", "Strain", "<.0001†", "B6", "C"], ["C57BL/6J-C3H/HeJ", ".262", "Stage*strain", "<.0001†", "C3H", "A"], ["PC6", "2.27 (74.8)", "C57BL/6J-A/J", ".130", "Stage", "<.0001†", "AJ", "B"], ["A/J-C3H/HeJ", ".231", "Strain", "<.0001†", "B6", "A"], ["C57BL/6J-C3H/HeJ", ".214", "Stage*strain", "0.0006†", "C3H", "B"], ["PC7", "2.02 (76.8)", "C57BL/6J-A/J", ".522***", "Stage", "<.0001†", "AJ", "A"], ["A/J-C3H/HeJ", ".561***", "Strain", "<.0001†", "B6", "B"], ["C57BL/6J-C3H/HeJ", ".734***", "Stage*strain", "0.0385", "C3H", "A"], ["PC8", "1.55 (78.4)", "C57BL/6J-A/J", ".286", "Stage", "<.0001†", "AJ", "B"], ["A/J-C3H/HeJ", ".469***", "Strain", "<.0001†", "B6", "A"], ["C57BL/6J-C3H/HeJ", ".131", "Stage*strain", "0.0437", "C3H", "A"], ["PC9", "1.43 (79.8)", "C57BL/6J-A/J", ".344*", "Stage", "<.0001†", "AJ", "B"], ["A/J-C3H/HeJ", ".479***", "Strain", "<.0001†", "B6", "C"], ["C57BL/6J-C3H/HeJ", ".194", "Stage*strain", "<.0001†", "C3H", "A"], ["PC10", "1.08 (80.9)", "C57BL/6J-A/J", ".320", "Stage", "<.0001†", "AJ", "C"], ["A/J-C3H/HeJ", ".386**", "Strain", "<.0001†", "B6", "B"], ["C57BL/6J-C3H/HeJ", ".181", "Stage*strain", "<.0001†", "C3H", "A"]], "row_count": 31, "column_count": 8, "numeric_cells": 91, "header_rows": 1, "locator": "section[6]/table-wrap[1]#table-1"}}, {"id": "asset:table:pmid:27602285:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:0bc9995f64303792194e3926b83026261cc59d71dab2a70c6ee1fb416418d9ec", "bytes": 1176, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[1]#table-2", "version": null, "note": "Summary of strain-dependent expression patterns for lung development transcriptional profiling in three inbred mouse strains.Four classes of strain-dependent gene expression account for the strain effects observed on PC 4–10. The percentage of genes in each of the four classes is based on total number of genes with significant strain-differences by Tukey HSD (Q < 0.05). The patterns within classes reflect the expression levels of genes in the outlier strain relative to the indistinguishable strains. The percentages of genes for each pattern are based on the total of genes in the parent class.", "structure": {"pmcid": "PMC4991849", "section_index": 15, "section_title": "Strain-specific patterns of gene expression during lung development", "row_count": 9, "column_count": 3}, "table": {"label": "Table 2", "caption": "Summary of strain-dependent expression patterns for lung development transcriptional profiling in three inbred mouse strains.Four classes of strain-dependent gene expression account for the strain effects observed on PC 4–10. The percentage of genes in each of the four classes is based on total number of genes with significant strain-differences by Tukey HSD (Q < 0.05). The patterns within classes reflect the expression levels of genes in the outlier strain relative to the indistinguishable strains. The percentages of genes for each pattern are based on the total of genes in the parent class.", "rows": [["Classes (4)", "Patterns"], ["C3H≠AJ≈B6", "C3H > AJ ≈ B6", "C3H < AJ ≈ B6"], ["223 genes (28.6%)", "89 genes (39.9%)", "134 genes (60.1%)"], ["B6≠AJ≈C3H", "B6 > C3H ≈ AJ", "B6 < C3H ≈ AJ"], ["349 genes (44.7%)", "142 genes (40.7%)", "207 genes (59.3%)"], ["AJ≠B6≈C3H", "AJ > B6 ≈ C3H", "AJ < B6 ≈ C3H"], ["152 genes (19.5%)", "85 genes (55.9%)", "67 genes (44.1%)"], ["C3H≠AJ≠B6", "", ""], ["57 genes (7.3%)", "", ""]], "row_count": 9, "column_count": 3, "numeric_cells": 11, "header_rows": 1, "locator": "section[15]/table-wrap[1]#table-2"}}, {"id": "asset:table:pmid:27602285:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:6f6d2a38cb362e2250bc83f84ff54f78524d48033aa716c953f7f8c4611f006f", "bytes": 3367, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[19]/table-wrap[1]#table-3", "version": null, "note": "Summary of Reactome pathway enrichment results for the 771 genes represented in both mouse and human embryonic developing lung characteristic subtranscriptomes.Entities refer to proteins, molecules, sequences, and other physical complexes associated with a given pathway in Reactome database; entities found are those associated with input gene sets and total entities refers to all entities in a given pathway. FDR represents multiple testing corrected p-values for enrichment.", "structure": {"pmcid": "PMC4991849", "section_index": 19, "section_title": "Comparative analysis of the mouse and human embryonic developing lung characteristic subtranscriptomes", "row_count": 45, "column_count": 5}, "table": {"label": "Table 3", "caption": "Summary of Reactome pathway enrichment results for the 771 genes represented in both mouse and human embryonic developing lung characteristic subtranscriptomes.Entities refer to proteins, molecules, sequences, and other physical complexes associated with a given pathway in Reactome database; entities found are those associated with input gene sets and total entities refers to all entities in a given pathway. FDR represents multiple testing corrected p-values for enrichment.", "rows": [["", "Entities found", "Entities total", "Percent total", "FDR"], ["Cell cycle", "92", "608", "15.1%", "8.97 × 10−14"], ["Cell cycle checkpoints", "22", "169", "13.0%", "1.80 × 10−2"], ["ATR response to replication stress", "8", "39", "20.5%", "4.77 × 10−2"], ["Mitotic G1-G1/S phases", "21", "139", "15.1%", "4.46 × 10−3"], ["Pre-replicative complex activation", "8", "33", "24.2%", "2.76 × 10−2"], ["Mitotic G2-G2/M phases", "23", "141", "16.3%", "7.50 × 10−4"], ["Polo-like kinase-mediated events", "9", "23", "39.1%", "6.70 × 10−4"], ["S phase", "16", "140", "11.4%", "9.08 × 10−2"], ["M phase", "51", "316", "16.1%", "2.84 × 10−8"], ["Resolution chromatid cohesion", "27", "128", "21.1%", "1.83 × 10−6"], ["Metabolism", "135", "3,163", "4.3%", "1.00 × 101"], ["Erythrocyte gas exchange", "4", "16", "25.0%", "1.40 × 10−1"], ["Surfactant metabolism", "7", "52", "13.5%", "1.96 × 10−1"], ["Immune system", "132", "1,841", "7.2%", "6.69 × 10−2"], ["Adaptive immune system", "75", "1,002", "7.5%", "1.18 × 10−1"], ["TCR signaling", "25", "145", "17.2%", "1.63 × 10−4"], ["MHC-II antigen presentation", "30", "141", "21.3%", "3.20 × 10−7"], ["Costimulation by CD28 family", "24", "96", "25.0%", "5.42 × 10−7"], ["PD-1 signaling", "17", "45", "37.8%", "3.20 × 10−7"], ["Cytokine signaling in immunity", "68", "678", "10.0%", "5.66 × 10−4"], ["Interferon signaling", "35", "289", "12.1%", "2.43 × 10−3"], ["Interferon gamma signaling", "21", "138", "15.2%", "3.77 × 10−2"], ["Antiviral mechanism IFN-stimulated", "13", "83", "15.7%", "3.60 × 10−2"], ["Interleukin signaling", "31", "358", "8.7%", "1.56 × 10−1"], ["DAP12 signaling", "33", "364", "9.1%", "9.02 × 10−2"], ["Developmental biology", "86", "904", "9.5%", "8.68 × 10−6"], ["Axon guidance", "66", "568", "11.6%", "8.68 × 10−6"], ["L1CAM interactions", "16", "124", "12.9%", "5.66 × 10−2"], ["NCAM signaling (neurite out-growth)", "29", "298", "9.7%", "6.69 × 10−2"], ["Semaphorin interactions", "11", "73", "15.1%", "6.69 × 10−2"], ["Signaling by robo receptor", "8", "38", "21.1%", "4.44 × 10−2"], ["Signal transduction", "211", "2,710", "7.79%", "3.42 × 10−1"], ["PIP3 Activates AKT sgnaling", "15", "121", "12.4%", "6.69 × 10−2"], ["IRS-mediated sgnaling", "28", "306", "9.2%", "1.21 × 10−1"], ["SCF-KIT sgnaling", "34", "339", "10.0%", "3.94 × 10−2"], ["EGFR signaling", "38", "376", "10.1%", "2.76 × 10−2"], ["FGFR signaling", "33", "356", "9.3%", "7.44 × 10−2"], ["PDGF signaling", "38", "392", "9.7%", "3.88 × 10−2"], ["ERBB2 signaling", "33", "360", "9.2%", "8.04 × 10−2"], ["ERBB4 signaling", "34", "345", "9.9%", "4.77 × 10−2"], ["Rho GT pase signaling", "64", "418", "15.3%", "1.52 × 10−9"], ["NGF signaling", "43", "478", "9.0%", "6.29 × 10−2"], ["Wnt signaling", "35", "326", "10.7%", "1.74 × 10−2"], ["IGF1R signaling", "29", "311", "9.3%", "9.40 × 10−2"]], "row_count": 45, "column_count": 5, "numeric_cells": 179, "header_rows": 1, "locator": 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