RNA-sequencing reveals positional memory of multipotent mesenchymal stromal cells from oral and maxillofacial tissue transcriptomes
RNA-sequencing reveals positional memory of multipotent mesenchymal stromal cells from oral and maxillofacial tissue transcriptomes
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DOI：
10.1186/s12864-020-06825-2
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发表时间：
2020-06-22
期刊：
影响因子：
4.4
通讯作者：
Iwata, Takanori
中科院分区：
文献类型：
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作者：
Onizuka, Satoru;Yamazaki, Yasuharu;Iwata, Takanori
背景多能间充质基质细胞（MSC）可以从多种组织中分离出来，并且由于其免疫调节和促再生能力而成为临床治疗应用的有吸引力的候选者。尽管定义 MSC 的最低标准已经确定，但已知它们的特征会根据其来源组织的不同而有所不同。结果我们从三种不同的骨骼（髂骨 (I-MSC)、上颌骨 (Mx-MSC) 和下颌骨 (Md-MSC)）中分离和表征了人类 MSC，并进行了下一代 RNA 测序。此外，为了研究其他细胞类型的基因表达谱，我们从序列读取档案中获取了人胚胎干细胞（ESC）和几种类型的 MSC（牙周膜来源的 MSC、骨髓来源的 MSC 和 ESC 来源的 MSC）的 RNA 序列数据，并分析了转录组谱。我们发现，源自颌面区域组织（例如颌骨和牙周膜）的间充质干细胞呈HOX阴性，而源自其他组织的间充质干细胞则呈HOX阳性。我们还发现，颅面部发育的重要调节因子 MSX1、LHX8 和 BARX1 在颌面部组织来源的 MSC 中强烈表达。虽然MSCs可以分为两个不同的组，细胞是否起源于颈部以上，但根据基因表达谱的差异，不同类型的MSCs中所有CD抗原基因的表达模式相似，除了ESCs。结论我们的研究结果表明，来自不同解剖位置的MSCs尽管满足一般特征标准，但在基因表达和位置记忆方面具有显着差异。尽管来自不同解剖来源的基质细胞通常被归类为间充质干细胞，但它们的分化潜力和生物学功能有所不同。我们认为间充质干细胞可能保留有关发育过程的原始组织记忆，包括基因表达谱。这可能会对选择合适的细胞来源进行间充质干细胞再生治疗产生重要影响。
BackgroundMultipotent mesenchymal stromal cells (MSCs) can be isolated from numerous tissues and are attractive candidates for therapeutic clinical applications due to their immunomodulatory and pro-regenerative capacity. Although the minimum criteria for defining MSCs have been defined, their characteristics are known to vary depending on their tissue of origin.ResultsWe isolated and characterized human MSCs from three different bones (ilium (I-MSCs), maxilla (Mx-MSCs) and mandible (Md-MSCs)) and proceeded with next generation RNA-sequencing. Furthermore, to investigate the gene expression profiles among other cell types, we obtained RNA-seq data of human embryonic stem cells (ESCs) and several types of MSCs (periodontal ligament-derived MSCs, bone marrow-derived MSCs, and ESCs-derived MSCs) from the Sequence Reads Archive and analyzed the transcriptome profile. We found that MSCs derived from tissues of the maxillofacial region, such as the jaw bone and periodontal ligament, were HOX-negative, while those derived from other tissues were HOX-positive. We also identified that MSX1, LHX8, and BARX1, an essential regulator of craniofacial development, were strongly expressed in maxillofacial tissue-derived MSCs. Although MSCs may be divided into two distinct groups, the cells originated from over the neck or not, on the basis of differences in gene expression profile, the expression patterns of all CD antigen genes were similar among different type of MSCs, except for ESCs.ConclusionsOur findings suggest that MSCs from different anatomical locations, despite meeting general characterization criteria, have remarkable differences in gene expression and positional memory. Although stromal cells from different anatomical sources are generally categorized as MSCs, their differentiation potential and biological functions vary. We suggested that MSCs may retain an original tissue memory about the developmental process, including gene expression profiles. This could have an important impact when choosing an appropriate cell source for regenerative therapy using MSCs.