{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T16:06:49Z","timestamp":1780330009589,"version":"3.54.1"},"reference-count":63,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Project of China","award":["2024YFF1206600"],"award-info":[{"award-number":["2024YFF1206600"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JDB"],"abstract":"<jats:p>Lung organogenesis is orchestrated by dynamic epithelial\u2013mesenchymal interactions during embryogenesis, yet the gene regulatory programs and signaling dynamics governing these processes in the pseudoglandular stage remain incompletely understood. In this study, we integrated spatial and single-cell transcriptomic data across embryonic developmental stages to systematically characterize epithelial and mesenchymal dynamics during lung development. To achieve more refined cell types at single-cell resolution in spatial transcriptomic data, we developed a bin-based deconvolution strategy that enabled high-precision cell-type assignment. We subsequently constructed a 3D spatiotemporal landscape of lung development and elucidated the molecular regulatory mechanisms underlying epithelial\u2013mesenchymal maturation during lung morphogenesis. In addition, we analyzed transcription factor module activity, intercellular communication signaling, and predicted downstream target genes, while integrating public GWAS metadata to link developmental programs with lung cancer-related features. We observed pronounced stage-specific functional heterogeneity between the pseudoglandular and late embryonic stages. Notably, E13.5 emerged as a critical transition window, during which progenitor states shifted toward more mature cellular phenotypes. We reconstructed epithelial\u2013mesenchymal interactions and uncovered coordinated rewiring of ligand\u2013receptor signaling and transcriptional networks across developmental stages. Regulatory network analysis further identified temporally coordinated transcription factor modules centered on Tbx3, Tbx5, Gli1, Gata4\/5, Foxa1\/2, and Cebpa, which collectively orchestrated branching morphogenesis, epithelial patterning, and tissue stabilization. Integration with lung cancer genome-wide association data demonstrated that embryonic lung progenitor states exhibit strong associations with lung cancer-related transcriptional programs, particularly involving epithelial\u2013mesenchymal plasticity and RNA-splicing pathways. Furthermore, TP53\/HNRNP-mutant lung adenocarcinomas displayed embryonic-like molecular features associated with cytoskeletal remodeling and progenitor-state reactivation. Together, our study provided a spatiotemporally resolved framework of embryonic lung development and identifies a critical transition window linking lung morphogenesis, regulatory network remodeling, and cancer-associated epithelial plasticity.<\/jats:p>","DOI":"10.3390\/jdb14020025","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T15:07:52Z","timestamp":1780326472000},"page":"25","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatiotemporal Profiling Defines the Epithelial and Mesenchymal Transition Window in Embryonic Lung Morphogenesis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2972-4268","authenticated-orcid":false,"given":"Huiwen","family":"Zheng","sequence":"first","affiliation":[{"name":"College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China"},{"name":"Key Laboratory of Spatial Omics of Zhejiang Province, BGI Research, Hangzhou 310030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5163-2895","authenticated-orcid":false,"given":"Jinpei","family":"Lin","sequence":"additional","affiliation":[{"name":"College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China"},{"name":"Key Laboratory of Spatial Omics of Zhejiang Province, BGI Research, Hangzhou 310030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanyi","family":"Li","sequence":"additional","affiliation":[{"name":"BGI Research, Shenzhen 518083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9845-3101","authenticated-orcid":false,"given":"Shijie","family":"Hao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Spatial Omics of Zhejiang Province, BGI Research, Hangzhou 310030, China"},{"name":"State Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Hangzhou 310030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengnan","family":"Cheng","sequence":"additional","affiliation":[{"name":"College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China"},{"name":"Key Laboratory of Spatial Omics of Zhejiang Province, BGI Research, Hangzhou 310030, China"},{"name":"State Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Hangzhou 310030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1152\/physrev.00028.2006","article-title":"Transcriptional control of lung morphogenesis","volume":"87","author":"Maeda","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1242\/dev.098186","article-title":"Lung development: Orchestrating the generation and regeneration of a complex organ","volume":"141","author":"Herriges","year":"2014","journal-title":"Development"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.devcel.2009.12.010","article-title":"Preparing for the first breath: Genetic and cellular mechanisms in lung development","volume":"18","author":"Morrisey","year":"2010","journal-title":"Dev. Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1042\/CS20080068","article-title":"Thyroid transcription factor-1 (TTF-1\/Nkx2. 1\/TITF1) gene regulation in the lung","volume":"116","author":"Boggaram","year":"2009","journal-title":"Clin. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1038\/5096","article-title":"Fgf10 is essential for limb and lung formation","volume":"21","author":"Sekine","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3731","DOI":"10.1242\/dev.096560","article-title":"Localized Fgf10 expression is not required for lung branching morphogenesis but prevents differentiation of epithelial progenitors","volume":"140","author":"Volckaert","year":"2013","journal-title":"Development"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Jiang, S., Li, Q., Liu, Y., Zhang, H., Wang, Q., Chen, Y., Shi, X., Li, J., Zhang, H., and Zhang, Y. (2021). Activation of WNT7b autocrine eases metastasis of colorectal cancer via epithelial to mesenchymal transition and predicts poor prognosis. BMC Cancer, 21.","DOI":"10.1186\/s12885-021-07898-2"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/S0960-9822(98)70446-4","article-title":"Sonic hedgehog regulates branching morphogenesis in the mammalian lung","volume":"8","author":"Pepicelli","year":"1998","journal-title":"Curr. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"De Langhe, S.P., Carraro, G., Tefft, D., Li, C., Xu, X., Chai, Y., Minoo, P., Hajihosseini, M.K., Drouin, J., and Kaartinen, V. (2008). Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by \u03b2-catenin signaling. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0001516"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"E4456","DOI":"10.1073\/pnas.1311847110","article-title":"Sox9 plays multiple roles in the lung epithelium during branching morphogenesis","volume":"110","author":"Rockich","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1146\/annurev-cellbio-100109-104040","article-title":"Epithelial progenitor cells in lung development, maintenance, repair, and disease","volume":"27","author":"Rock","year":"2011","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6636","DOI":"10.1038\/s41467-021-26950-0","article-title":"Sequence logic at enhancers governs a dual mechanism of endodermal organ fate induction by FOXA pioneer factors","volume":"12","author":"Geusz","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4831","DOI":"10.1242\/dev.129.20.4831","article-title":"Wnt7b regulates mesenchymal proliferation and vascular development in the lung","volume":"129","author":"Shu","year":"2002","journal-title":"Development"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"L823","DOI":"10.1152\/ajplung.2001.280.5.L823","article-title":"Transcription factors in mouse lung development and function","volume":"280","author":"Costa","year":"2001","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/s41580-022-00531-5","article-title":"Organization, dynamics and mechanoregulation of integrin-mediated cell\u2013ECM adhesions","volume":"24","author":"Kanchanawong","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"528","DOI":"10.4161\/cam.22862","article-title":"The role of extracellular matrix in vascular branching morphogenesis","volume":"6","author":"Mettouchi","year":"2012","journal-title":"Cell Adhes. Migr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nrclinonc.2010.196","article-title":"Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways","volume":"8","author":"Takebe","year":"2011","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s12943-023-01744-8","article-title":"Extracellular matrix remodeling in tumor progression and immune escape: From mechanisms to treatments","volume":"22","author":"Yuan","year":"2023","journal-title":"Mol. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/nrc.2017.118","article-title":"EMT in cancer","volume":"18","author":"Brabletz","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1038\/s41587-023-01697-9","article-title":"High-resolution alignment of single-cell and spatial transcriptomes with CytoSPACE","volume":"41","author":"Vahid","year":"2023","journal-title":"Nat. Biotechnol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1561\/2200000073","article-title":"Computational optimal transport: With applications to data science","volume":"11","author":"Cuturi","year":"2019","journal-title":"Found. Trends\u00ae  Mach. Learn."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","article-title":"Dictionary learning for integrative, multimodal and scalable single-cell analysis","volume":"42","author":"Hao","year":"2024","journal-title":"Nat. Biotechnol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1038\/s41467-021-21246-9","article-title":"Inference and analysis of cell-cell communication using CellChat","volume":"12","author":"Jin","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/s41592-019-0667-5","article-title":"NicheNet: Modeling intercellular communication by linking ligands to target genes","volume":"17","author":"Browaeys","year":"2020","journal-title":"Nat. Methods"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1038\/s41596-020-0336-2","article-title":"A scalable SCENIC workflow for single-cell gene regulatory network analysis","volume":"15","author":"Flerin","year":"2020","journal-title":"Nat. Protoc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1093\/bioinformatics\/bty916","article-title":"GRNBoost2 and Arboreto: Efficient and scalable inference of gene regulatory networks","volume":"35","author":"Moerman","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1002\/wics.147","article-title":"ggplot2","volume":"3","author":"Wickham","year":"2011","journal-title":"Wiley Interdiscip. Rev. Comput. Stat."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1016\/j.cell.2022.04.003","article-title":"Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays","volume":"185","author":"Chen","year":"2022","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1038\/s41586-024-07069-w","article-title":"A single-cell time-lapse of mouse prenatal development from gastrula to birth","volume":"626","author":"Qiu","year":"2024","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"dev199512","DOI":"10.1242\/dev.199512","article-title":"A single-cell atlas of mouse lung development","volume":"148","author":"Negretti","year":"2021","journal-title":"Development"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/s41586-020-2822-7","article-title":"Capillary cell-type specialization in the alveolus","volume":"586","author":"Gillich","year":"2020","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3903","DOI":"10.1073\/pnas.1621177114","article-title":"Transcription factor Etv5 is essential for the maintenance of alveolar type II cells","volume":"114","author":"Zhang","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.ydbio.2008.04.006","article-title":"A regulatory relationship between Tbx1 and FGF signaling during tooth morphogenesis and ameloblast lineage determination","volume":"320","author":"Mitsiadis","year":"2008","journal-title":"Dev. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Zuo, W.-L., Rostami, M.R., LeBlanc, M., Kaner, R.J., O\u2019Beirne, S.L., Mezey, J.G., Leopold, P.L., Quast, K., Visvanathan, S., and Fine, J.S. (2020). Dysregulation of club cell biology in idiopathic pulmonary fibrosis. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0237529"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/JVI.00030-19","article-title":"PPAR-\u03b3 in macrophages limits pulmonary inflammation and promotes host recovery following respiratory viral infection","volume":"93","author":"Huang","year":"2019","journal-title":"J. Virol."},{"key":"ref_36","first-page":"1245","article-title":"Got: An optimal transport framework for graph comparison","volume":"32","author":"Chierchia","year":"2019","journal-title":"Adv. Neural Inf. Process. Syst."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1165\/ajrcmb.24.1.4040","article-title":"Triggering the induction of myofibroblast and fibrogenesis by airway epithelial shedding","volume":"24","author":"Morishima","year":"2001","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"12444","DOI":"10.1073\/pnas.1406639111","article-title":"Wnt ligand\/Frizzled 2 receptor signaling regulates tube shape and branch-point formation in the lung through control of epithelial cell shape","volume":"111","author":"Kadzik","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.ydbio.2007.04.033","article-title":"Fgf10 dosage is critical for the amplification of epithelial cell progenitors and for the formation of multiple mesenchymal lineages during lung development","volume":"307","author":"Ramasamy","year":"2007","journal-title":"Dev. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8334","DOI":"10.1038\/s41598-018-26673-1","article-title":"Spatial and temporal changes in extracellular elastin and laminin distribution during lung alveolar development","volume":"8","author":"Luo","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1242\/dev.015495","article-title":"Wnt7b stimulates embryonic lung growth by coordinately increasing the replication of epithelium and mesenchyme","volume":"135","author":"Rajagopal","year":"2008","journal-title":"Development"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1165\/rcmb.2015-0128PS","article-title":"Alveolar development and disease","volume":"53","author":"Whitsett","year":"2015","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1161\/CIRCRESAHA.108.181818","article-title":"Branching morphogenesis","volume":"103","author":"Horowitz","year":"2008","journal-title":"Circ. Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Nyeng, P., Norgaard, G.A., Kobberup, S., and Jensen, J. (2008). FGF10 maintains distal lung bud epithelium and excessive signaling leads to progenitor state arrest, distalization, and goblet cell metaplasia. BMC Dev. Biol., 8.","DOI":"10.1186\/1471-213X-8-2"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3405","DOI":"10.1242\/dev.01913","article-title":"Gata4 expression in lateral mesoderm is downstream of BMP4 and is activated directly by Forkhead and GATA transcription factors through a distal enhancer element","volume":"132","author":"Rojas","year":"2005","journal-title":"Development"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0012-1606(02)00026-X","article-title":"Transcriptional activation of BMP-4 and regulation of mammalian organogenesis by GATA-4 and-6","volume":"254","author":"Nemer","year":"2003","journal-title":"Dev. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"8425","DOI":"10.1074\/jbc.M110.202150","article-title":"Dual functions of T-box 3 (Tbx3) in the control of self-renewal and extraembryonic endoderm differentiation in mouse embryonic stem cells","volume":"286","author":"Lu","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.ceb.2015.08.005","article-title":"Rho GTPase signalling in cell migration","volume":"36","author":"Ridley","year":"2015","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4148","DOI":"10.1038\/s41467-024-48632-3","article-title":"CEBPA restricts alveolar type 2 cell plasticity during development and injury-repair","volume":"15","author":"Hassan","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"E10615","DOI":"10.1073\/pnas.1811624115","article-title":"Evolutionarily conserved Tbx5\u2013Wnt2\/2b pathway orchestrates cardiopulmonary development","volume":"115","author":"Steimle","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1478-811X-8-23","article-title":"Rac and Rho GTPases in cancer cell motility control","volume":"8","author":"Parri","year":"2010","journal-title":"Cell Commun. Signal."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1002\/ijc.32932","article-title":"Potentially functional genetic variants in PLIN2, SULT2A1 and UGT1A9 genes of the ketone pathway and survival of nonsmall cell lung cancer","volume":"147","author":"Tang","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1513\/pats.200801-006AW","article-title":"Lung epithelial progenitor cells: Lessons from development","volume":"5","author":"Rawlins","year":"2008","journal-title":"Proc. Am. Thorac. Soc."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1038\/s41586-025-08757-x","article-title":"Spatially resolved mapping of cells associated with human complex traits","volume":"641","author":"Song","year":"2025","journal-title":"Nature"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1158\/1055-9965.EPI-16-0794","article-title":"A decade of GWAS results in lung cancer","volume":"27","author":"Amos","year":"2018","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13059-018-1416-2","article-title":"Single-cell RNA-seq analysis unveils a prevalent epithelial\/mesenchymal hybrid state during mouse organogenesis","volume":"19","author":"Dong","year":"2018","journal-title":"Genome Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41422-023-00802-6","article-title":"Single-cell RNA sequencing reveals the developmental program underlying proximal\u2013distal patterning of the human lung at the embryonic stage","volume":"33","author":"Cao","year":"2023","journal-title":"Cell Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"aaa5838","DOI":"10.1126\/science.aaa5838","article-title":"BMP gradients: A paradigm for morphogen-mediated developmental patterning","volume":"348","author":"Bier","year":"2015","journal-title":"Science"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1203\/01.PDR.0000159570.01327.ED","article-title":"Molecular mechanisms of early lung specification and branching morphogenesis","volume":"57","author":"Warburton","year":"2005","journal-title":"Pediatr. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1126\/science.284.5420.1635","article-title":"Genetic control of branching morphogenesis","volume":"284","author":"Metzger","year":"1999","journal-title":"Science"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12931-021-01617-y","article-title":"Potential interactions between the TBX4-FGF10 and SHH-FOXF1 signaling during human lung development revealed using ChIP-seq","volume":"22","author":"Karolak","year":"2021","journal-title":"Respir. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1234850","DOI":"10.1126\/science.1234850","article-title":"Epithelial plasticity: A common theme in embryonic and cancer cells","volume":"342","author":"Nieto","year":"2013","journal-title":"Science"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Kang, D.H., Kim, Y., Lee, J.H., Kang, H.S., and Chung, C. (2025). Spatial transcriptomics in lung cancer and pulmonary diseases: A comprehensive review. Cancers, 17.","DOI":"10.3390\/cancers17121912"}],"container-title":["Journal of Developmental Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2221-3759\/14\/2\/25\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T15:34:42Z","timestamp":1780328082000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2221-3759\/14\/2\/25"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,1]]},"references-count":63,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["jdb14020025"],"URL":"https:\/\/doi.org\/10.3390\/jdb14020025","relation":{},"ISSN":["2221-3759"],"issn-type":[{"value":"2221-3759","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,1]]}}}