A Subpopulation of Schwann Cell-Like Cells With Nerve Regeneration Signatures Is Identified Through Single-Cell RNA Sequencing

Abstract

Schwann cell-like cells (SCLCs) derived from human amniotic mesenchymal stem cells (hAMSCs) have been shown to promote peripheral nerve regeneration, but the underlying molecular mechanism was still poorly understood. In order to investigate the heterogeneity and potential molecular mechanism of SCLCs in the treatment of peripheral nerve regeneration at a single cell level, single-cell RNA sequencing was applied to profile single cell populations of hAMSCs and SCLCs. We profiled 6,008 and 5,140 single cells from hAMSCs and SCLCs, respectively. Based on bioinformatics analysis, pathways associated with proliferation, ECM organization, and tissue repair were enriched within both populations. Cell cycle analysis indicated that single cells within these two populations remained mostly in the G0/G1 phase. The transformation of single cells from hAMSCs to SCLCs was characterized by pseudotime analysis. Furthermore, we identified a subpopulation of SCLCs that highly expressed genes associated with Schwann cell proliferation, migration, and survival, such as JUN, JUND, and NRG1., Genes such as PTGS2, PITX1, VEGFA, and FGF2 that promote nerve regeneration were also highly expressed in single cells within this subpopulation, and terms associated with inflammatory and tissue repair were enriched in this subpopulation by pathway enrichment analysis. Our results indicate that a subpopulation of SCLCs with nerve regeneration signatures may be the key populations that promote nerve regeneration.

Using a Transection Paradigm to Enhance the Repair Mechanisms of an Investigational Human Cell Therapy

“…The data clustered into 10 cell groups and were defined based on characteristic genes in previously published single cell data for each particular cell type (Fig. 2C) [32][33][34][35][36][37][38][39][40][41] . -Cell counts were obtained from the single nuclei RNA seq analysis and each cluster's percentage was reported (Fig.…”

A novel induced pluripotent stem cell model of Schwann cell differentiation revealsNF2- related gene regulatory networks of the extracellular matrix

“…Single cell RNA-seq (scRNA-seq) data from human amniotic mesenchymal stem cells (hAMSCs) differentiated to Schwann like cells (SLCs) was downloaded from Gene Expression Omnibus (GSE161066) [29]. The Seurat R package [34] was used for initial data cleaning and quality control, removing cells with < than 200 or > 2,500 unique feature counts as well as cells with > 5 percent mitochondrial RNAs.…”

“…We further refine the putative roles of these modules using functional enrichment analysis [28]. To validate our findings, we compared the DEGs and gene modules derived from our hiPSC induced Schwann cells with two independent single cell and bulk transcriptomic datasets of human Schwann cell differentiation [29] and mouse sciatic nerve development [30].…”

scRNA‐seq and proteomics reveal the distinction of M2‐like macrophages between primary and recurrent malignant glioma and its critical role in the recurrence

“…[41][42][43] According to expression of differential genes, the subgroups of malignant cells were annotated as follows: (1) the MES-like malignant cells with high expression of VIM; (2) the OPC-like malignant cells characterized with high OLIG1, ALCAM and PLP1 expression; (3) the NPC-like malignant cells highly expressing SOX4, SOX11 and DCX; (4) the malignant cells related to proliferation expressing the proliferation markers MKI67, CENPF, TOP2A (Figure 3B-D). 42,44,45 We found that markers of AC-like cells (GFAP, S100B, SLC1A3) were widely expressed in each subgroup, so none of the subgroups was annotated as AC-like malignant cells (Figure 3C,D). 42 Interestingly, we noticed that another mesenchymal marker CD44 was highly expressed only in clusters 0 and 4 but not in cluster 6 (Figure 3C,D).…”