Human Wharton's Jelly Mesenchymal Stem Cells Show Unique Gene Expression Compared with Bone Marrow Mesenchymal Stem Cells Using Single-Cell RNA-Sequencing
Human Wharton's Jelly Mesenchymal Stem Cells Show Unique Gene Expression Compared with Bone Marrow Mesenchymal Stem Cells Using Single-Cell RNA-Sequencing
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DOI：
10.1089/scd.2018.0132
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发表时间：
2019-02-01
影响因子：
4
通讯作者：
Bongso, Ariff
中科院分区：
文献类型：
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作者：
Barrett, Angela N.;Fong, Chui-Yee;Bongso, Ariff
从人脐带中分离的人脐带胶质干细胞（hWJSC）是具有显著临床用途的独特的间充质干细胞（MSC）群体。它们广泛的分化潜力，高增殖率，易于从丢弃的脐带中获得，以及在培养中长期维持干细胞特性，使它们成为与人骨髓间充质干细胞（hBMMSCs）相比具有治疗价值的有吸引力的替代MSC来源。我们的目的是使用单细胞RNA测序（scRNA-Seq）来表征这两种干细胞类型之间基因表达谱的差异，以确定哪些途径参与赋予hWJSC其独特特性。我们确定了436个在两种细胞类型之间显著差异表达的基因，这些基因在免疫调节、血管生成、伤口愈合、凋亡、抗肿瘤活性和趋化性等过程中发挥作用。与hBMMSC相比，hWJSC中免疫分子的表达特别高。这些基因表达的差异可能有助于解释hWJSC在临床应用中相对于hBMMSC的许多优势。尽管细胞表面蛋白标志物表达表明分离的hWJSC和hBMMSC都是同质群体，但使用scRNA-Seq，我们可以清楚地鉴定出特定细胞类型内单个细胞之间表达水平的极端变异性。如果将细胞作为整体群体进行检查，则不可能理解单个细胞可能对表观总体表达水平做出主要独特贡献。我们证明了hWJSC和hBMMSC内表达的微调如何通过在两个细胞之间表达具有相反功能的分子来实现。我们假设，更好地了解这两种细胞类型之间的基因表达差异可能有助于开发使用hWJSC的新疗法。
Human Wharton's jelly stem cells (hWJSCs) isolated from the human umbilical cord are a unique population of mesenchymal stem cells (MSCs) with significant clinical utility. Their broad differentiation potential, high rate of proliferation, ready availability from discarded cords, and prolonged maintenance of stemness properties in culture make them an attractive alternative source of MSCs with therapeutic value compared with human bone marrow MSCs (hBMMSCs). We aimed to characterize the differences in gene expression profiles between these two stem cell types using single-cell RNA sequencing (scRNA-Seq) to determine which pathways are involved in conferring hWJSCs with their unique properties. We identified 436 significantly differentially expressed genes between the two cell types, playing roles in processes, including immunomodulation, angiogenesis, wound healing, apoptosis, antitumor activity, and chemotaxis. Expression of immune molecules is particularly high in hWJSCs compared with hBMMSCs. These differences in gene expression may help to explain many of the advantages that hWJSCs have over hBMMSCs for clinical application. Although cell surface protein marker expression indicates that isolated hWJSCs and hBMMSCs are both homogenous populations, using scRNA-Seq we can clearly identify extreme variability in expression levels between individual cells within a certain cell type. If the cells are examined as bulk populations, it is not possible to appreciate that a single cell may be making a major unique contribution to the apparent overall expression level. We demonstrated how the fine tuning of expression within hWJSCs and hBMMSCs may be achieved by expression of molecules with opposing function between two cells. We hypothesize that a greater understanding of these differences in gene expression between the two cell types may aid in the development of new therapies using hWJSCs.