Cell Therapy Area, Department of Hematology, Institute of Biomedical Research of Salamanca-Hospital Universitario de Salamanca (IBSAL-HUS), 37007 Salamanca, Spain.
Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Institute of Biomedical Research of Salamanca-Hospital Universitario de Salamanca (IBSAL-HUS), 37007 Salamanca, Spain.
Int J Mol Sci. 2024 Nov 6;25(22):11906. doi: 10.3390/ijms252211906.
In this paper, we present a comparative analysis of the transcriptomic profile of three different human cell types: hematopoietic stem cells (HSCs), bone marrow-derived mesenchymal stem cells (MSCs) and fibroblasts (FIBs). The work aims to identify unique genes that are differentially expressed as specific markers of bone marrow-derived MSCs, and to achieve this undertakes a detailed analysis of three independent datasets that include quantification of the global gene expression profiles of three primary cell types: HSCs, MSCs and FIBs. A robust bioinformatics method, called , is used to assess the specific association between one or more genes expressed in a sample and the outcome variable, that is, the 'cell type' provided as a single univariate response. This outcome variable is predicted for each sample tested, based on the expression profile of the specific genes that are used as input to the test. The precision of the tests is calculated along with the statistical sensitivity and specificity for each gene in each dataset, yielding four genes that mark MSCs with high accuracy. Among these, the best performer is the protein-coding gene Transgelin (TAGLN, Gene ID: 6876) (with a Positive Predictive Value > 0.96 and FDR < 0.001), which identifies MSCs better than any of the currently used standard markers: ENG (CD105), THY1 (CD90) or NT5E (CD73). The results are validated by RT-qPCR, providing novel gene biomarkers specific for human MSCs.
在本文中，我们对三种不同的人类细胞类型的转录组谱进行了比较分析：造血干细胞（HSCs）、骨髓间充质干细胞（MSCs）和成纤维细胞（FIBs）。这项工作旨在鉴定出作为骨髓间充质干细胞特异性标记物差异表达的独特基因，并为此对三个独立数据集进行了详细分析，其中包括对三种原代细胞（HSCs、MSCs 和 FIBs）的全局基因表达谱进行定量。使用一种称为 的稳健生物信息学方法来评估在样本中表达的一个或多个基因与作为单一单变量反应提供的“细胞类型”之间的特定关联。基于用作测试输入的特定基因的表达谱，对每个测试样本进行此结果变量的预测。针对每个数据集计算了测试的精度，以及每个基因的统计灵敏度和特异性，从而产生了四个可高度准确标记 MSC 的基因。其中，表现最好的是编码蛋白的 Transgelin（TAGLN，基因 ID：6876）（阳性预测值>0.96，FDR<0.001），其识别 MSC 的性能优于任何当前使用的标准标记物：ENG（CD105）、THY1（CD90）或 NT5E（CD73）。通过 RT-qPCR 进行了验证，为人类 MSC 提供了新的基因生物标志物。
