1 research outputs found
Sca-1 is a marker for cell plasticity in murine pancreatic epithelial cells and induced by IFN-β in vitro
BACKGROUND & AIMS: Sca-1 is a surface marker for murine hematopoietic stem cells (HSCs) and type-I interferon is a key regulator for LinSca-1 HSCs expansion through Ifnar/Stat-1/Sca-1-signaling. In this study we aimed to characterize the role and regulation of Sca-1 cells in pancreatic regeneration.
METHODS: To characterize Sca-1 in vivo, immunohistochemistry and immunofluorescence staining of Sca-1 was conducted in normal pancreas, in cerulein-mediated acute pancreatitis, and in Kras-triggered cancerous lesions. Ifnar/Stat-1/Sca-1-signaling was studied in type-I IFN-treated epithelial explants of adult wildtype, Ifnar, and Stat-1 mice. Sca-1 induction was analyzed by gene expression and FACS analysis. After isolation of pancreatic epithelial LinSca-1cells, pancreatosphere-formation and immunofluorescence-assays were carried out to investigate self-renewal and differentiation capabilities.
RESULTS: Sca-1 cells were located in periacinar and periductal spaces and showed an enrichment during cerulein-induced acute pancreatitis (23.2/100 μm ± 4.9 SEM) and in early inflammation-mediated carcinogenic lesions of the pancreas of Kras mice (35.8/100 μm ± SEM 1.9) compared to controls (3.6/100 μm ± 1.3 SEM). Pancreatic LinSca-1 cells displayed a small population of 1.46% ± 0.12 SEM in FACS. In IFN-β treated pancreatic epithelial explants, Sca-1 expression was increased, and LinSca-1 cells were enriched in vitro (from 1.49% ± 0.36 SEM to 3.85% ± 0.78 SEM). LinSca-1 cells showed a 12 to 51-fold higher capacity for clonal self-renewal compared to LinSca-1 cells and generated cells express markers of the acinar and ductal compartment.
CONCLUSIONS: Pancreatic Sca-1 cells enriched during parenchymal damage showed a significant capacity for cell renewal and in vitro plasticity, suggesting that corresponding to the type I interferon-dependent regulation of LinSca-1 hematopoietic stem cells, pancreatic Sca-1 cells also employ type-I-interferon for regulating progenitor-cell-homeostasis