{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:27:17Z","timestamp":1785403637818,"version":"3.56.0"},"reference-count":47,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273734"],"award-info":[{"award-number":["82273734"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82304250"],"award-info":[{"award-number":["82304250"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82273734"],"award-info":[{"award-number":["82273734"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82304250"],"award-info":[{"award-number":["82304250"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bulk RNA-sequencing (bulk RNA-seq) averages gene expression across cell mixtures, obscuring single-cell heterogeneity and spatial architectures essential for understanding pathological processes. We developed HistoMap, a deep learning-based framework for single-cell spatial deconvolution. The model employs a two-stage pipeline: first, reconstructing high-fidelity single-cell profiles from bulk data using a \u03b2-variational autoencoder, and second, utilizing a Histological Vision Transformer (H-ViT) to map these cells to tissue coordinates via dual guidance from transcriptomic references and H&amp;E-stained morphological constraints. HistoMap demonstrated superior performance across diverse human tissues, achieving a Pearson Correlation Coefficient (PCC) of 0.800 on external validation. Application to 14 colorectal cancer cases revealed a Macro_SPP1-mediated desmoplastic barrier. SPP1+ macrophages act as spatial hubs at the invasive front, forming a physical \u201csequestration belt\u201d that functionally excludes cytotoxic T cells from the tumor core. HistoMap successfully bridges bulk RNA-seq and spatial single-cell architectures. Our findings provide a molecular rationale for immune checkpoint blockade resistance and identify the SPP1-fibroblast axis as a pivotal target for therapeutic sensitization.<\/jats:p>","DOI":"10.3390\/ijms27125259","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T02:59:31Z","timestamp":1781146771000},"page":"5259","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["HistoMap: Reconstructing Spatially Resolved Single-Cell Profiles from Bulk RNA-Seq to Decipher the Immune-Excluded Microenvironment in Colon Cancer"],"prefix":"10.3390","volume":"27","author":[{"given":"Jia","family":"He","sequence":"first","affiliation":[{"name":"Department of Biostatistics, School of Public Health, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, School of Public Health, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1437-7231","authenticated-orcid":false,"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, School of Public Health, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, School of Public Health, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxin","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, School of Public Health, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hesong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, School of Public Health, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongzhen","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, School of Public Health, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6718-5212","authenticated-orcid":false,"given":"Qiuju","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, School of Public Health, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, School of Public Health, Harbin Medical University, Harbin 150081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1038\/s41576-021-00370-8","article-title":"Integrating single-cell and spatial transcriptomics to elucidate intercellular tissue dynamics","volume":"22","author":"Longo","year":"2021","journal-title":"Nat. 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