» Articles » PMID: 35047019

Single-Cell and Bulk Transcriptome Data Integration Reveals Dysfunctional Cell Types and Aberrantly Expressed Genes in Hypertrophic Scar

Overview
Journal Front Genet
Date 2022 Jan 20
PMID 35047019
Authors
Affiliations
Soon will be listed here.
Abstract

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.

Citing Articles

Isorhamnetin inhibits hypertrophic scar formation through TGF-β1/Smad and TGF-β1/CREB3L1 signaling pathways.

Wu J, Song Y, Wang J, Wang T, Yang L, Shi Y Heliyon. 2024; 10(13):e33802.

PMID: 39055792 PMC: 11269880. DOI: 10.1016/j.heliyon.2024.e33802.


The Molecular Mechanisms Involved in the Hypertrophic Scars Post-Burn Injury.

Pradhan M, Pethe P Yale J Biol Med. 2024; 96(4):549-563.

PMID: 38161582 PMC: 10751863. DOI: 10.59249/RHUF5686.


Deciphering the contributions of cuproptosis in the development of hypertrophic scar using single-cell analysis and machine learning techniques.

Song B, Liu W, Zhu Y, Peng Y, Cui Z, Gao B Front Immunol. 2023; 14:1207522.

PMID: 37409114 PMC: 10318401. DOI: 10.3389/fimmu.2023.1207522.


The Secretome of Irradiated Peripheral Mononuclear Cells Attenuates Hypertrophic Skin Scarring.

Vorstandlechner V, Copic D, Klas K, Direder M, Golabi B, Radtke C Pharmaceutics. 2023; 15(4).

PMID: 37111549 PMC: 10143262. DOI: 10.3390/pharmaceutics15041065.


Pan-cancer analysis of CREB3L1 as biomarker in the prediction of prognosis and immunotherapeutic efficacy.

Lin Z, Wu Y, Xiao X, Zhang X, Wan J, Zheng T Front Genet. 2022; 13:938510.

PMID: 36171879 PMC: 9511413. DOI: 10.3389/fgene.2022.938510.


References
1.
Lee J, Yang C, Chao S, Wong T . Histopathological differential diagnosis of keloid and hypertrophic scar. Am J Dermatopathol. 2004; 26(5):379-84. DOI: 10.1097/00000372-200410000-00006. View

2.
Limandjaja G, van den Broek L, Breetveld M, Waaijman T, Monstrey S, de Boer E . Characterization of In Vitro Reconstructed Human Normotrophic, Hypertrophic, and Keloid Scar Models. Tissue Eng Part C Methods. 2018; 24(4):242-253. DOI: 10.1089/ten.TEC.2017.0464. View

3.
Yamamoto A, Morioki H, Nakae T, Miyake Y, Harada T, Noda S . Transcription factor old astrocyte specifically induced substance is a novel regulator of kidney fibrosis. FASEB J. 2020; 35(2):e21158. PMC: 7821213. DOI: 10.1096/fj.202001820R. View

4.
Love M, Huber W, Anders S . Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014; 15(12):550. PMC: 4302049. DOI: 10.1186/s13059-014-0550-8. View

5.
Feng Y, Wu J, Sun Z, Liu S, Zou M, Yuan Z . Targeted apoptosis of myofibroblasts by elesclomol inhibits hypertrophic scar formation. EBioMedicine. 2020; 54:102715. PMC: 7132150. DOI: 10.1016/j.ebiom.2020.102715. View