Transcriptomic and Proteomic Profiling of Human Mesenchymal Stem Cell Derived from Umbilical Cord in the Study of Preterm Birth

Mesenchymal stem cells (MSCs) hold great therapeutic potential in morbidities associated with preterm birth. However, the molecular expressions of hMSCs in preterm birth infants have not been systematically evaluated. In this study, we presented the dual-omics analyses of umbilical cord (UC) derived hMSCs to identify the dysregulated cellular functions. Materials and methods: The UC-MSCs were collected from 10 full-term and 8 preterm birth infants for transcriptomics and proteomics analyses by using microarray and iTRAQ-based proteome profiling. The integrative analysis of dual-omics data discovered 5,615 commonly identified genes/proteins of which 29 genes/proteins showed consistent up- or down-regulation in preterm birth. The Gene Ontology analysis revealed that the biological processes of mitochondrial translation and cellular response to oxidative stress were mainly enriched in 290 differential expression proteins (DEPs) while the 421 differential expression genes (DEGs) were majorly involved in secondary alcohol metabolic process, cellular response to stress, and mitotic cell cycle in preterm birth. Besides, we identified a 13-protein module involving CUL2 and CUL3, which plays an important role in cullin-RING-based ubiquitin ligase complex, as potential mechanism for preterm birth. The dual-omics data not only provided new insights to the molecular mechanism but also to identify panel of candidate markers associated with preterm birth.

间充质干细胞（mesenchymal stem cells, MSCs）在与早产相关的多种病症中具有显著的治疗潜力。然而，早产婴儿来源的人类间充质干细胞（human mesenchymal stem cells, hMSCs）的分子表达谱尚未得到系统评估。
本研究针对脐带（umbilical cord, UC）来源的hMSCs开展双组学分析，以鉴定失调的细胞功能。
材料与方法：本研究收集了10名足月产婴儿与8名早产婴儿的脐带间充质干细胞（UC-MSCs），通过基因芯片技术与基于同位素标记相对和绝对定量（isobaric tags for relative and absolute quantitation, iTRAQ）的蛋白质组分析，完成转录组学与蛋白质组学检测。
对双组学数据的整合分析共鉴定出5615个共同检出的基因/蛋白质，其中29个基因/蛋白质在早产样本中呈现一致的上调或下调表达。
基因本体（Gene Ontology, GO）分析显示，290个差异表达蛋白质（differentially expressed proteins, DEPs）主要富集于线粒体翻译、细胞氧化应激应答等生物学过程；而421个差异表达基因（differentially expressed genes, DEGs）则主要参与次级醇代谢、细胞应激应答及有丝分裂细胞周期等过程。
此外，本研究鉴定出一个包含CUL2与CUL3的13蛋白模块，该模块参与Cullin-RING型泛素连接酶复合物的功能调控，可作为早产发生的潜在分子机制。
本双组学数据不仅为早产的分子机制研究提供了新见解，还为筛选与早产相关的候选标志物组提供了重要依据。