肌成纤维细胞
成纤维细胞
转录组
生物
纤维化
祖细胞
细胞生物学
人口
病理
癌症研究
干细胞
医学
细胞培养
基因表达
遗传学
基因
环境卫生
作者
Tracy Tabib,Meng Huang,Nina Morse,Anna Papazoglou,Rithika Behera,Minxue Jia,Melissa Bulik,Daisy Monier,Panayiotis V. Benos,Wei Chen,Robyn T. Domsic,Robert Lafyatis
标识
DOI:10.1038/s41467-021-24607-6
摘要
Abstract Skin and lung fibrosis in systemic sclerosis (SSc) is driven by myofibroblasts, alpha-smooth muscle actin expressing cells. The number of myofibroblasts in SSc skin correlates with the modified Rodnan skin score, the most widely used clinical measure of skin disease severity. Murine fibrosis models indicate that myofibroblasts can arise from a variety of different cell types, but their origin in SSc skin has remained uncertain. Utilizing single cell RNA-sequencing, we define different dermal fibroblast populations and transcriptome changes, comparing SSc to healthy dermal fibroblasts. Here, we show that SSc dermal myofibroblasts arise in two steps from an SFRP2 hi /DPP4 -expressing progenitor fibroblast population. In the first step, SSc fibroblasts show globally upregulated expression of transcriptome markers, such as PRSS23 and THBS1 . A subset of these cells shows markers indicating that they are proliferating. Only a fraction of SFRP2 hi SSc fibroblasts differentiate into myofibroblasts, as shown by expression of additional markers, SFRP4 and FNDC1 . Bioinformatics analysis of the SSc fibroblast transcriptomes implicated upstream transcription factors, including FOSL2 , RUNX1 , STAT1, FOXP1, IRF7 and CREB3L1 , as well as SMAD3 , driving SSc myofibroblast differentiation.
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