Dataset Information

The transcriptional profile of keloidal Schwann cells.

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.

SUBMITTER: Direder M

PROVIDER: S-EPMC9722693 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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The transcriptional profile of keloidal Schwann cells.

Direder Martin M Wielscher Matthias M Weiss Tamara T Laggner Maria M Copic Dragan D Klas Katharina K Bormann Daniel D Vorstandlechner Vera V Tschachler Erwin E Jan Ankersmit Hendrik H Mildner Michael M

Experimental & molecular medicine 20221104 11

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 ...[more]

PMID: 36333467

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Project description:BackgroundSchwann cells (SCs) are primarily responsible for regeneration and repair of the peripheral nervous system (PNS). Renewable and lineage-restricted SC precursors (SCPs) are considered highly desirable and promising cell sources for the production of SCs and for studies of SC lineage development, but SCPs are extremely limited. Here, we present a novel direct conversion strategy for the generation of human SCPs, capable of differentiating into functional SCs.MethodsEasily accessible human skin fibroblast cells were directly induced into integration-free SCPs using episomal vectors (Oct3/4, Klf4, Sox2, L-Myc, Lin28 and p53 shRNA) under SCP lineage-specific chemically defined medium conditions. Induced SCPs (iSCPs) were further examined for their ability to differentiate into SCs. The identification and functionality of iSCPs and iSCP-differentiated SCs (iSCs) were confirmed according to morphology, lineage-specific markers, neurotropic factor secretion, and/or standard functional assays.ResultsHighly pure, Sox 10-positive of iSCPs (more than 95% purity) were generated from human skin fibroblasts within 3 weeks. Established iSCPs could be propagated in vitro while maintaining their SCP identity. Within 1 week, iSCPs could efficiently differentiate into SCs (more than 95% purity). The iSCs were capable of secreting various neurotrophic factors such as GDNF, NGF, BDNF, and NT-3. The in vitro myelinogenic potential of iSCs was assessed by myelinating cocultures using mouse dorsal root ganglion (DRG) neurons or human induced pluripotent stem cell (iPSC)-derived sensory neurons (HSNs). Furthermore, iSC transplantation promoted sciatic nerve repair and improved behavioral recovery in a mouse model of sciatic nerve crush injury in vivo.ConclusionsWe report a robust method for the generation of human iSCPs/iSCs that might serve as a promising cellular source for various regenerative biomedical research and applications, such as cell therapy and drug discovery, especially for the treatment of PNS injury and disorders.

Project description:Methyl jasmonate (MeJA) has been successfully used as an effective elicitor to enhance production of taxol and other taxanes in cultured Taxus cells. However the mechanism of MeJA-mediated taxane biosynthesis remains unclear. Genomic information for species in the genus Taxus is currently unavailable. Therefore, information about the transcriptome of Taxus cells and specifically, description of changes in gene expression in response to MeJA, is needed for the better exploration of the biological mechanisms of MeJA-mediated taxane biosynthesis.In this research, the transcriptome profiles of T. chinensis cells at 16 hours (T16) after MeJA treatment and of mock-treated cells (T0) were analyzed by "RNA-seq" to investigate the transcriptional alterations of Taxus cell in response to MeJA elicitation. More than 58 million reads (200 bp in length) of cDNA from both samples were generated, and 46,581 unigenes were found. There were 13,469 genes found to be expressed differentially between the two timepoints, including all of the known jasmonate (JA) biosynthesis/JA signaling pathway genes and taxol-related genes. The qRT-PCR results showed that the expression profiles of 12 randomly selected DEGs and 10 taxol biosynthesis genes were found to be consistent with the RNA-Seq data. MeJA appeared to stimulate a large number of genes involved in several relevant functional categories, such as plant hormone biosynthesis and phenylpropanoid biosynthesis. Additionally, many genes encoding transcription factors were shown to respond to MeJA elicitation.The results of a transcriptome analysis suggest that exogenous application of MeJA could induce JA biosynthesis/JA signaling pathway/defence responses, activate a series of transcription factors, as well as increase expression of genes in the terpenoid biosynthesis pathway responsible for taxol synthesis. This comprehensive description of gene expression information could greatly facilitate our understanding of the molecular mechanisms of MeJA-mediated taxane biosynthesis in Taxus cells.

Dataset Information

The transcriptional profile of keloidal Schwann cells.

Publications

The transcriptional profile of keloidal Schwann cells.

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