Identifying heterogeneity of Schwann cell like cells via scRNA-seq.

Previously we have reported that Schwann cell like cells (SCLCs) induced from human amniotic mesenchymal stem cells (hAMSCs) have better peripheral nerve regeneration ability, but the heterogeneity of SCLCs is still poorly understood. Here, based on single-cell RNA sequencing, we investigated the heterogeneity of hAMSCs and SCLCs, and identified the transition from hAMSCs to SCLCs. Totally 6,008 and 5,140 cells generated from hAMSCs and SCLCs were profiled and used for deep analysis. A subpopulation of SCLCs highly expressed Schwann cell markers, JUN, JUND, and NRG1, was identified. Then, cell cycle analysis distinguished the proliferation state of each cluster, and single cells of the subpopulation in SCLCs mainly remained in G0/G1 phase. Pseudotime analysis illustrated how hAMSCs transformed into SCLCs, hAMSCs showed more possibility transformed into other cell types. Through marker gene identification, pathway enrichment, transcription factor analysis, and secreted protein validation, genes such as NRG1, PTGS2, PITX1, VEGFA, and FGF2 were highly expressed in single cells. And also, pathways associated with nerve regeneration and immune control were enriched, such as angiogenesis or TNF signaling.

此前我们已有研究报道，由人羊膜间充质干细胞（human amniotic mesenchymal stem cells, hAMSCs）诱导获得的施万细胞样细胞（Schwann cell like cells, SCLCs）具备更优异的外周神经再生能力，但目前对SCLCs的细胞异质性仍缺乏深入认知。本研究基于单细胞RNA测序（single-cell RNA sequencing），对hAMSCs与SCLCs的细胞异质性展开系统探究，并明确了hAMSCs向SCLCs的细胞转化过程。研究共对来源于hAMSCs的6008个细胞与来源于SCLCs的5140个细胞进行了测序表征与深度分析。我们鉴定得到一个高表达施万细胞标志物的SCLCs亚群，该亚群显著高表达JUN、JUND及NRG1基因。随后通过细胞周期分析区分了各细胞簇的增殖状态，结果显示该SCLCs亚群中的单个细胞主要停滞于G0/G1期。拟时分析（Pseudotime analysis）阐明了hAMSCs向SCLCs的转化轨迹，同时发现hAMSCs具备更高的向其他细胞类型转化的潜能。通过标志物基因鉴定、通路富集分析、转录因子分析以及分泌蛋白验证，我们发现NRG1、PTGS2、PITX1、VEGFA与FGF2等基因在单个细胞中呈高表达水平。此外，与神经再生和免疫调控相关的通路如血管生成（angiogenesis）、TNF信号通路（TNF signaling）等亦呈现显著富集。

搜集汇总

背景与挑战

背景概述

该数据集通过单细胞RNA测序技术，研究人类羊膜间充质干细胞诱导的施万细胞样细胞的异质性，识别出高表达施万细胞标记物的亚群，并揭示其与神经再生相关的基因和通路。数据集包含2个样本，来自20-30岁人类个体，使用Illumina平台进行转录组测序，旨在促进对神经再生机制的理解。