Uncovering stem cell differentiation factors for salivary gland regeneration by quantitative analysis of differential proteomes.
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.
Department of Oral and Maxillofacial Diagnostic Sciences, University of Florida College of Dentistry, Gainesville, FL, United States of America.
Yun-Jong
YJ
Park
Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, FL, United States of America.
Jin
J
Koh
Department of Oral and Maxillofacial Diagnostic Sciences, University of Florida College of Dentistry, Gainesville, FL, United States of America.
Jin Teak
JT
Kwon
Department of Oral Anatomy, Seoul National University School of Dentistry, Seoul, Korea.
Yong-Seok
YS
Park
Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, United States of America.
Lijun
L
Yang
Department of Oral and Maxillofacial Diagnostic Sciences, University of Florida College of Dentistry, Gainesville, FL, United States of America.
Seunghee
S
Cha
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics / Q000528:radiation effects*; D002478:Cells, Cultured; D016000:Cluster Analysis; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D011788:Quality of Life; D012469:Salivary Glands / Q000378:metabolism* / Q000502:physiology; D053719:Tandem Mass Spectrometry; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D020543:Proteome; D014157:Transcription Factors; C446484:Ascl3 protein, mouse; C491312:Bhlha15 protein, mouse; C062602:transcription factor PTF1