Expression Profile of Isogenic Early Mesodermal Cells Differentiated from Human Induced Pluripotent Stem Cells

IF 0.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
A. V. Selezneva, E. V. Korobko, S. L. Kiselev, Yu. G. Suzdaltseva
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引用次数: 0

Abstract

Scar formation during normal regeneration of damaged tissue can lead to noticeable cosmetic and functional defects of organs and thus significantly affect the quality of life. Meanwhile, fetal tissues before the third trimester of pregnancy are known to be capable of complete regeneration with the restoration of the original architecture and functional activity. Understanding the cellular and molecular mechanisms of fetal wound regeneration will provide the basis for the development of successful treatments aimed to minimize scarring. Mesenchymal stromal cells (MSCs) play an important role in tissue repair, since cytokines, chemokines, growth factors and extracellular vesicles they secrete are involved in the regulation of migration, angiogenesis, synthesis, and remodeling of the extracellular matrix. Mesodermal differentiation of human induced pluripotent stem cells (iPSCs) enables to reproduce consecutive stages of embryogenesis in vitro and to create isogenic cell models of MSCs, corresponding to different stages of human development. Here, we performed a specifically directed, multistage, mesodermal differentiation of iPSCs into isogenic cell lines of the primitive streak, lateral and paraxial mesoderm, as well as carried out a comparative analysis of their expression profiles. It was shown that the derived cells of the lateral mesoderm (LM) and paraxial mesoderm (PM) are precursors for MSCs. The MSCs, derived due to differentiation of both LM and PM cells, shared a similar expression profile of pan-mesodermal markers. A comparative analysis of the functional activity of MSCs and their precursors in a pro-inflammatory microenvironment will hopefully provide molecular tools for a better insight into the basic mechanisms of fetal tissue regeneration and help identify therapeutic targets to minimize scarring and pathological processes characterized by excessive fibroplasia.

Abstract Image

从人类诱导多能干细胞分化出的同源早期中胚层细胞的表达谱
摘要 在受损组织的正常再生过程中,疤痕的形成会导致器官出现明显的外观和功能缺陷,从而严重影响生活质量。与此同时,已知怀孕三个月前的胎儿钙组织可以完全再生,恢复原有的结构和功能活性。了解胎儿伤口再生的细胞和分子机制将为开发成功的治疗方法提供基础,从而最大限度地减少瘢痕。间充质基质细胞(MSCs)在组织修复中发挥着重要作用,因为它们分泌的细胞因子、趋化因子、生长因子和细胞外囊泡参与调节细胞外基质的迁移、血管生成、合成和重塑。人类诱导多能干细胞(iPSCs)的中胚层分化可在体外再现胚胎发育的连续阶段,并创建对应人类不同发育阶段的间充质干细胞同源细胞模型。在这里,我们对 iPSCs 进行了有针对性的多阶段中胚层分化,将其分化成原始条纹、侧中胚层和副中胚层的同源细胞系,并对它们的表达谱进行了比较分析。结果表明,侧中胚层(LM)和轴旁中胚层(PM)的衍生细胞是间充质干细胞的前体。由侧中胚层细胞和副中胚层细胞分化而来的间充质干细胞具有相似的泛中胚层标志物表达谱。对间叶干细胞及其前体细胞在促炎症微环境中的功能活性进行比较分析,有望为更好地了解胎儿组织再生的基本机制提供分子工具,并有助于确定治疗靶点,以尽量减少以过度纤维增生为特征的瘢痕和病理过程。
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来源期刊
自引率
33.30%
发文量
110
审稿时长
6-12 weeks
期刊介绍: Journal of Evolutionary Biochemistry and Physiology  publishes original experimental and theoretical and review articles related to evolution of the main forms of metabolism in connection with life origin; comparative and ontogenetic physiology and biochemistry, biochemical evolution of animal world; as well as evolution of functions; morphology, pharmacology, pathophysiology and ecological physiology. The journal welcomes manuscripts from all countries in the English or Russian language.
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