Sca-1 is a marker for cell plasticity in murine pancreatic epithelial cells and induced by IFN-β in vitro.

Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 2022 Mar

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Sca-1 is a surface marker for murine hematopoietic stem cells (HSCs) and type-I interferon is a key regulator for Lin-Sca-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. 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 Lin-Sca-1+cells, pancreatosphere-formation and immunofluorescence-assays were carried out to investigate self-renewal and differentiation capabilities. Sca-1+ cells were located in periacinar and periductal spaces and showed an enrichment during cerulein-induced acute pancreatitis (23.2/100 μm2 ± 4.9 SEM) and in early inflammation-mediated carcinogenic lesions of the pancreas of KrasG12D mice (35.8/100 μm2 ± SEM 1.9) compared to controls (3.6/100 μm2 ± 1.3 SEM). Pancreatic Lin-Sca-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 Lin-Sca-1+ cells were enriched in vitro (from 1.49% ± 0.36 SEM to 3.85% ± 0.78 SEM). Lin-Sca-1+ cells showed a 12 to 51-fold higher capacity for clonal self-renewal compared to Lin-Sca-1- cells and generated cells express markers of the acinar and ductal compartment. 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 Lin-Sca-1+ hematopoietic stem cells, pancreatic Sca-1+ cells also employ type-I-interferon for regulating progenitor-cell-homeostasis. Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.

Citation

Georg Leinenkugel, Bo Kong, Susanne Raulefs, Katharina Miller, Susanne Roth, Hongdie Jiang, Rouzanna Istvánffy, Hanna Heikenwälder, Nadja Maeritz, Ivonne Regel, Ivane Abiatari, Jörg Kleeff, Christoph W Michalski, Simon Rieder. Sca-1 is a marker for cell plasticity in murine pancreatic epithelial cells and induced by IFN-β in vitro. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]. 2022 Mar;22(2):294-303