TY - JOUR TI - Visualization of stem cell activity in pancreatic cancer expansion by direct lineage tracing with live imaging AU - Maruno, Takahisa AU - Fukuda, Akihisa AU - Goto, Norihiro AU - Tsuda, Motoyuki AU - Ikuta, Kozo AU - Hiramatsu, Yukiko AU - Ogawa, Satoshi AU - Nakanishi, Yuki AU - Yamaga, Yuichi AU - Yoshioka, Takuto AU - Takaori, Kyoichi AU - Uemoto, Shinji AU - Saur, Dieter AU - Chiba, Tsutomu AU - Seno, Hiroshi A2 - White, Richard M A2 - Macleod, Kay F VL - 10 PY - 2021 DA - 2021/01/04 SP - e55117 C1 - eLife 2021;10:e55117 DO - 10.7554/eLife.55117 UR - https://doi.org/10.7554/eLife.55117 AB - Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease. Although rigorous efforts identified the presence of ‘cancer stem cells (CSCs)’ in PDAC and molecular markers for them, stem cell dynamics in vivo have not been clearly demonstrated. Here we focused on Doublecortin-like kinase 1 (Dclk1), known as a CSC marker of PDAC. Using genetic lineage tracing with a dual-recombinase system and live imaging, we showed that Dclk1+ tumor cells continuously provided progeny cells within pancreatic intraepithelial neoplasia, primary and metastatic PDAC, and PDAC-derived spheroids in vivo and in vitro. Furthermore, genes associated with CSC and epithelial mesenchymal transition were enriched in mouse Dclk1+ and human DCLK1-high PDAC cells. Thus, we provided direct functional evidence for the stem cell activity of Dclk1+ cells in vivo, revealing the essential roles of Dclk1+ cells in expansion of pancreatic neoplasia in all progressive stages. KW - pancreatic adenocarcinoma KW - genetic lineage tracing KW - live imaging KW - cancer stem cells JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -