The transcriptional profile of keloidal Schwann cells
4
조회
0
다운로드
1
인용
0
참고문헌
초록
Recently, a specific Schwann cell type with profibrotic and tissue regenerative properties that contributes to keloid formation has been identified. In the present study, we reanalyzed published single-cell RNA sequencing (scRNA-seq) studies of keloids, healthy skin, and normal scars to reliably determine the specific gene expression profile of keloid-specific Schwann cell types in more detail. We were able to confirm the presence of the repair-like, profibrotic Schwann cell type in the datasets of all three studies and identified a specific gene-set for these Schwann cells. In contrast to keloids, in normal scars, the number of Schwann cells was not increased, nor was their gene expression profile distinctly different from that of Schwann cells of normal skin. In addition, our bioinformatics analysis provided evidence for a role of transcription factors of the AP1, STAT, and KLF families, and members of the IER genes in the dedifferentiation process of keloidal Schwann cells. Together, our analysis strengthens the role of the profibrotic Schwann cell type in the formation of keloids. Knowledge of the exact gene expression profile of these Schwann cells will facilitate their identification in other organs and diseases.
Abstract
Recently, a specific Schwann cell type with profibrotic and tissue regenerative properties that contributes to keloid formation has been identified. In the present study, we reanalyzed published single-cell RNA sequencing (scRNA-seq) studies of keloids, healthy skin, and normal scars to reliably determine the specific gene expression profile of keloid-specific Schwann cell types in more detail. We were able to confirm the presence of the repair-like, profibrotic Schwann cell type in the datasets of all three studies and identified a specific gene-set for these Schwann cells. In contrast to keloids, in normal scars, the number of Schwann cells was not increased, nor was their gene expression profile distinctly different from that of Schwann cells of normal skin. In addition, our bioinformatics analysis provided evidence for a role of transcription factors of the AP1, STAT, and KLF families, and members of the IER genes in the dedifferentiation process of keloidal Schwann cells. Together, our analysis strengthens the role of the profibrotic Schwann cell type in the formation of keloids. Knowledge of the exact gene expression profile of these Schwann cells will facilitate their identification in other organs and diseases.
참고문헌 (60)
- Bhatheja, K., "Schwann cells : origins and role in axonal maintenance and regeneration", Int. J. Biochem. Cell Biol, 38, pp.1995~1999 (2006)
- Jessen, K. R., "The role of cell plasticity in tissue repair:adaptive cellular reprogramming", Dev. Cell, 34, pp.613~620 (2015)
- Weiss, T., "Proteomics and transcriptomics of peripheral nerve tissue and cells unravel new aspects of the human Schwann cell repair phenotype", Glia, 64, pp.2133~2153 (2016)
- Jessen, K. R., "The success and failure of the schwann cell response to nerve injury", Front. Cell. Neurosci, 13, pp.33~ (2019)
- Bosse, F., "Gene expression profiling reveals that peripheral nerve regeneration is a consequence of both novel injurydependent and reactivated developmental processes", J. Neurochem, 96, pp.1441~1457 (2006)
- Parfejevs, V., "Injury-activated glial cells promote wound healing of the adult skin in mice", Nat. Commun, 9, pp.236~ (2018)
- Gomez-Sanchez, J. A., "After nerve injury, lineage tracing shows that myelin and remak schwann cells elongate extensively and branch to form repair schwann cells, which shorten radically on remyelination", J. Neurosci, 37, pp.9086~9099 (2017)
- Murray, J. C., "Keloids and hypertrophic scars", Clin. Dermatol, 12, pp.27~37 (1994)
- Ud-Din, S., "New insights on keloids, hypertrophic scars, and striae", Dermatol. Clin, 32, pp.193~209 (2014)
- Balci, D. D., "DLQI scores in patients with keloids and hypertrophic scars: a prospective case control study", J. Dtsch. Dermatol. Ges, 7, pp.688~692 (2009)
- Alhady, S. M., "Keloids in various races. A review of 175 cases", Plast. Reconstr. Surg, 44, pp.564~566 (1969)
- Tuan, T. L., "The molecular basis of keloid and hypertrophic scar formation", Mol. Med. Today, 4, pp.19~24 (1998)
- Yang, G. P., "From scarless fetal wounds to keloids : molecular studies in wound healing", Wound Repair Regen, 11, pp.411~418 (2003)
- Limandjaja, G. C., "The keloid disorder:heterogeneity, histopathology, mechanisms and models", Front. Cell. Dev. Biol, 8, pp.360~ (2020)
- Liu, X., "Single-cell RNA-seq reveals lineage-specific regulatory changes of fibroblasts and vascular endothelial cells in keloids", J. Invest. Dermatol, 142, pp.124~135.e11 (2021)
- Deng, C. C., "Single-cell RNA-seq reveals fibroblast heterogeneity and increased mesenchymal fibroblasts in human fibrotic skin diseases", Nat. Commun, 12, pp.3709~ (2021)
- Direder, M., "Schwann cells contribute to keloid formation", Matrix Biol, 108, pp.55~76 (2022)
- Tabib, T., "SFRP2", DPP4 and FMO1, J. Invest. Dermatol, pp.2018, 138[DOI]
- Vorstandlechner, V., "Deciphering the functional heterogeneity of skin fibroblasts using single-cell RNA sequencing", Faseb J, 34, pp.3677~3692 (2020)
- Solé-Boldo, L., "Single-cell transcriptomes of the human skin reveal agerelated loss of fibroblast priming", Commun. Biol, 3, pp.188~ (2020)
- He, H., "Single-cell transcriptome analysis of human skin identifies novel fibroblast subpopulation and enrichment of immune subsets in atopic dermatitis", J. Allergy Clin. Immunol, 145, pp.1615~1628 (2020)
- Ascensión, A. M., "Human dermal fibroblast subpopulations are conserved across single-cell RNA sequencing studies", J. Invest. Dermatol, 141, pp.1735~1744.e1735 (2021)
- Zheng, G. X., "Massively parallel digital transcriptional profiling of single cells", Nat. Commun, 8, pp.14049~ (2017)
- Hao, Y., "Integrated analysis of multimodal single-cell data", Cell, 184, pp.3573~3587.e29 (2021)
- Ahlmann-Eltze, C., "glmGamPoi : fitting Gamma-Poisson generalized linear models on single cell count data", Bioinformatics, 36, pp.5701~5702 (2021)
- Hafemeister, C., "Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression", Genome Biol, 20, pp.296~ (2019)
- Bargagna-Mohan, P., "Corneal nonmyelinating Schwann cells illuminated by single-cell transcriptomics and visualized by protein biomarkers", J. Neurosci. Res, 99, pp.731~749 (2021)
- Zhou, Y., "Metascape provides a biologist-oriented resource for the analysis of systems-level datasets", Nat. Commun, 10, pp.1523~ (2019)
- Trapnell, C., "The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells", Nat. Biotechnol, 32, pp.381~386 (2014)
- Qiu, X., "Reversed graph embedding resolves complex single-cell trajectories", Nat. Methods, 14, pp.979~982 (2017)
- Cao, J., "The single-cell transcriptional landscape of mammalian organogenesis", Nature, 566, pp.496~502 (2019)
- Traag, V. A., "From Louvain to Leiden : guaranteeing well-connected communities", Sci. Rep, 9, pp.5233~ (2019)
- Levine, J. H., "Data-driven phenotypic dissection of AML reveals progenitorlike cells that correlate with prognosis", Cell, 162, pp.184~197 (2015)
- Jin, S., "Inference and analysis of cell-cell communication using CellChat", Nat. Commun, 12, pp.1088~ (2021)
- Xue, M., "Extracellular matrix reorganization during wound healing and its impact on abnormal scarring", Adv. Wound Care, 4, pp.119~136 (2015)
- Jessen, K. R., "The repair Schwann cell and its function in regenerating nerves", J. Physiol, 594, pp.3521~3531 (2016)
- van den Brink, S. C., "Single-cell sequencing reveals dissociation-induced gene expression in tissue subpopulations", Nat. Methods, 14, pp.935~936 (2017)
- Denisenko, E., "Systematic assessment of tissue dissociation and storage biases in single-cell and single-nucleus RNA-seq workflows", Genome Biol, 21, pp.130~ (2020)
- Fadl, B. R., "An optimized protocol for retina single-cell RNA sequencing", Mol. Vis, 26, pp.705~717 (2020)
- Reinisch, C. M., "The dimensions and characteristics of the subepidermal nerve plexus in human skin-terminal Schwann cells constitute a substantial cell population within the superficial dermis", J. Dermatol. Sci, 65, pp.162~169 (2012)
- Reinisch, C. M., "Rarefaction of the peripheral nerve network in diabetic patients is associated with a pronounced reduction of terminal Schwann cells", Diabetes Care, 31, pp.1219~1221 (2008)
- Vorstandlechner, V., "The serine proteases dipeptidyl-peptidase 4 and urokinase are key molecules in human and mouse scar formation", Nat. Commun, 12, pp.6242~ (2021)
- Weiss, T., "Detailed protocols for the isolation, culture, enrichment and immunostaining of primary human Schwann Cells", Methods Mol. Biol, 1739, pp.67~86 (2018)
- Andersen, N. D., "A rapid and versatile method for the isolation, purification and cryogenic storage of Schwann cells from adult rodent nerves", Sci. Rep, 6, pp.31781~ (2016)
- Silva, W. N., "Role of Schwann cells in cutaneous wound healing", Wound Repair Regen, 26, pp.392~397 (2018)
- Nagarajan, R., "Deciphering peripheral nerve myelination by using Schwann cell expression profiling", Proc. Natl Acad. Sci. U. S. A, 99, pp.8998~9003 (2002)
- Arthur-Farraj, P. J., "c-Jun reprograms Schwann cells of injured nerves to generate a repair cell essential for regeneration", Neuron, 75, pp.633~647 (2012)
- Barrette, B., "Transcriptional profiling of the injured sciatic nerve of mice carrying the Wld(S)mutant gene : identification of genes involved in neuroprotection, neuroinflammation, and nerve regeneration", Brain Behav. Immun, 24, pp.1254~1267 (2010)
- De Felipe, C., "The differential control of c-jun expression in regenerating sensory neurons and their associated glial cells", J. Neurosci, 14, pp.2911~2923 (1994)
- Shy, M. E., "Axon-Schwann cell interactions regulate the expression of c-jun in Schwann cells", J. Neurosci. Res, 43, pp.511~525 (1996)
- Parkinson, D. B., "Krox-20 inhibits Jun-NH2-terminal kinase", c-Jun to control Schwann cell proliferation and death, 2004, pp.164, 385~394
- Parkinson, D. B., "c-Jun is a negative regulator of myelination", J. Cell Biol, 181, pp.625~637 (2008)
- Fogarty, E. A., "SOX10-regulated promoter use defines isoform-specific gene expression in Schwann cells", BMC Genomics, 21, pp.549~ (2020)
- Widera, D., "Schwann cells can be reprogrammed to multipotency by culture", Stem Cells Dev, 20, pp.2053~2064 (2011)
- Gui, T., "Krüppel-like factor 6 rendered rat Schwann cell more sensitive to apoptosis via upregulating FAS expression", PLoS ONE, 8, pp.e82449~ (2013)
- Li, M., "Meta-analysis reveals transcription factor upregulation in cells of injured mouse sciatic nerve", Front. Cell. Neurosci, 15, pp.688243~ (2021)
- Wang, Y., "KLF7-transfected Schwann cell graft transplantation promotes sciatic nerve regeneration", Neuroscience, 340, pp.319~332 (2017)
- Mizuno, M., "Type I collagen-induced osteoblastic differentiation of bone-marrow cells mediated by collagen-alpha2beta1 integrin interaction", J. Cell. Physiol, 184, pp.207~213 (2000)
- Campbell, W. A., "Midkine is neuroprotective and influences glial reactivity and the formation of Müller glia-derived progenitor cells in chick and mouse retinas", Glia, 69, pp.1515~1539 (2021)
- Koutsioumpa, M., "Interplay between αvβ3 integrin and nucleolin regulates human endothelial and glioma cell migration", J. Biol. Chem, 288, pp.343~354 (2013)
