Elucidation of the mechanism of canceration derived from injured pancreatic acinar cells thorough developing two-step lineage-tracing system

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K18254
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory animal science; Digestive surgery
• Research Institution: Kansai Medical University
• Principal Investigator: ATSUMI Naho 関西医科大学, 医学部, 助教 (90612151)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 遺伝子改変マウス / 細胞系譜追跡 / 膵臓がん

Outline of Final Research Achievements

Elucidation of how pancreatic cancer develops is strongly needed, because of its bad prognosis and difficulty in its early detection due to lack of subjective symptoms. Chronic pancreatitis has been pointed out as one of the causes of pancreatic cancer, and acinar cells are considered as its origin based on the experiments using several mouse models.
We launched ourselves on histological and biological analysis of injured pancreatic acinar cells to study the possibility that the response of acinar cells to injury triggers caceration. For this purpose, we've developed two-step lineage-tracing system, which marks two different cellular states, such as undifferentiated and transit-amplifying ones, with two different fluorescent proteins and enables us to trace the cells with the two markers.

Free Research Field

腫瘍細胞生物学

Academic Significance and Societal Importance of the Research Achievements

2 段階細胞系譜追跡法では、2つの状態 (細胞種) を経験したことの目印をつけてその細胞の命運を追跡することで、生体内で多段階の分化系譜を規定できる。さらに、掛け合わせるドライバーマウスを替えることで、他の臓器の異なる現象にも応用可能だという意義がある。例えば、幹細胞あるいは前駆細胞を1段階目に、がん幹細胞を2段階目に標識・追跡することで、がんの起源細胞の同定につながる可能性がある。また、1段階目に幹細胞を、2段階目に前駆細胞マーカー候補陽性細胞を標識し、2つの標識を持つ細胞が終末分化細胞へと分化するかを調べることで、階層的な制御機構によって、器官が維持されているかを検証できる可能性がある。