Park Yun-Jong, Koh Jin, Kwon Jin Teak, Park Yong-Seok, Yang Lijun, Cha Seunghee
Department of Oral and Maxillofacial Diagnostic Sciences, University of Florida College of Dentistry, Gainesville, FL, United States of America.
Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, FL, United States of America.
PLoS One. 2017 Feb 3;12(2):e0169677. doi: 10.1371/journal.pone.0169677. eCollection 2017.
Severe xerostomia (dry mouth) compromises the quality of life in patients with Sjögren's syndrome or radiation therapy for head and neck cancer. A clinical management of xerostomia is often unsatisfactory as most interventions are palliative with limited efficacy. Following up our previous study demonstrating that mouse BM-MSCs are capable of differentiating into salivary epithelial cells in a co-culture system, we further explored the molecular basis that governs the MSC reprogramming by utilizing high-throughput iTRAQ-2D-LC-MS/MS-based proteomics. Our data revealed the novel induction of pancreas-specific transcription factor 1a (PTF1α), muscle, intestine and stomach expression-1 (MIST-1), and achaete-scute complex homolog 3 (ASCL3) in 7 day co-cultured MSCs but not in control MSCs. More importantly, a common notion of pancreatic-specific expression of PTF1 α was challenged for the first time by our verification of PTF1 α expression in the mouse salivary glands. Furthermore, a molecular network simulation of our selected putative MSC reprogramming factors demonstrated evidence for their perspective roles in salivary gland development. In conclusion, quantitative proteomics with extensive data analyses narrowed down a set of MSC reprograming factors potentially contributing to salivary gland regeneration. Identification of their differential/synergistic impact on MSC conversion warrants further investigation.
严重的口腔干燥症会影响干燥综合征患者或头颈部癌症放疗患者的生活质量。由于大多数干预措施只是姑息性的，疗效有限，因此口腔干燥症的临床管理往往不尽人意。在我们之前的研究表明小鼠骨髓间充质干细胞（BM-MSCs）在共培养系统中能够分化为唾液腺上皮细胞之后，我们利用基于高通量iTRAQ-2D-LC-MS/MS的蛋白质组学进一步探索了控制间充质干细胞重编程的分子基础。我们的数据显示，在共培养7天的间充质干细胞中，胰腺特异性转录因子1a（PTF1α）、肌肉、肠和胃表达-1（MIST-1）以及achaete-scute复合体同源物3（ASCL3）有新的诱导表达，但在对照间充质干细胞中没有。更重要的是，我们首次通过在小鼠唾液腺中验证PTF1α的表达，对PTF1α在胰腺中特异性表达的普遍观念提出了挑战。此外，对我们所选的假定间充质干细胞重编程因子进行的分子网络模拟证明了它们在唾液腺发育中的潜在作用。总之，通过广泛的数据分析进行的定量蛋白质组学研究，缩小了一组可能有助于唾液腺再生的间充质干细胞重编程因子的范围。确定它们对间充质干细胞转化的差异/协同影响值得进一步研究。
