{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:45:10Z","timestamp":1788432310964,"version":"build-2803163510"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T00:00:00Z","timestamp":1641168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Hypertrophic scar (HS) is a common skin disorder characterized by excessive extracellular matrix (ECM) deposition. However, it is still unclear how the cellular composition, cell-cell communications, and crucial transcriptionally regulatory network were changed in HS. In the present study, we found that FB-1, which was identified a major type of fibroblast and had the characteristics of myofibroblast, was significantly expanded in HS by integrative analysis of the single-cell and bulk RNA sequencing (RNA-seq) data. Moreover, the proportion of KC-2, which might be a differentiated type of keratinocyte (KC), was reduced in HS. To decipher the intercellular signaling, we conducted the cell-cell communication analysis between the cell types, and found the autocrine signaling of HB-1 through COL1A1\/2-CD44 and CD99-CD99 and the intercellular contacts between FB-1\/FB-5 and KC-2 through COL1A1\/COL1A2\/COL6A1\/COL6A2-SDC4. Almost all the ligands and receptors involved in the autocrine signaling of HB-1 were upregulated in HS by both scRNA-seq and bulk RNA-seq data. In contrast, the receptor of KC-2, SDC4, which could bind to multiple ligands, was downregulated in HS, suggesting that the reduced proportion of KC-2 and apoptotic phenotype of KC-2 might be associated with the downregulation of SDC4. Furthermore, we also investigated the transcriptionally regulatory network involved in HS formation. The integrative analysis of the scRNA-seq and bulk RNA-seq data identified CREB3L1 and TWIST2 as the critical TFs involved in the myofibroblast of HS. In summary, the integrative analysis of the single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data greatly improved our understanding of the biological characteristics during the HS formation.<\/jats:p>","DOI":"10.3389\/fgene.2021.806740","type":"journal-article","created":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T03:52:12Z","timestamp":1641181932000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Single-Cell and Bulk Transcriptome Data Integration Reveals Dysfunctional Cell Types and Aberrantly Expressed Genes in Hypertrophic Scar"],"prefix":"10.3389","volume":"12","author":[{"given":"Shunuo","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiru","family":"Min","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.matbio.2013.02.010","article-title":"Enhanced Deposition of Cartilage Oligomeric Matrix Protein Is a Common Feature in Fibrotic Skin Pathologies","volume":"32","author":"Agarwal","year":"2013","journal-title":"Matrix Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1038\/nmeth.4463","article-title":"SCENIC: Single-Cell Regulatory Network Inference and Clustering","volume":"14","author":"Aibar","year":"2017","journal-title":"Nat. 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