Randriamanantsoa Samuel J, Raich Marion K, Saur Dieter, Reichert Maximilian, Bausch Andreas R
Technical University of Munich, TUM School of Natural Sciences, Department of Bioscience, Chair for Cellular Biophysics E27, 85748 Garching, Germany.
Technical University of Munich, Center for Functional Protein Assemblies (CPA), 85748 Garching, Germany.
iScience. 2024 Jun 18;27(7):110299. doi: 10.1016/j.isci.2024.110299. eCollection 2024 Jul 19.
Lumens are crucial features of the tissue architecture in both the healthy exocrine pancreas, where ducts shuttle enzymes from the acini to the intestine, and in the precancerous lesions of the highly lethal pancreatic ductal adenocarcinoma (PDAC), similarly displaying lumens that can further develop into cyst-like structures. Branched pancreatic-cancer derived organoids capture key architectural features of both the healthy and diseased pancreas, including lumens. However, their transition from a solid mass of cells to a hollow tissue remains insufficiently explored. Here, we show that organoids display two orthogonal but complementary lumen formation mechanisms: one relying on fluid intake for multiple microlumen nucleation, swelling and fusion, and the other involving the death of a central cell population, thereby hollowing out cavities. These results shed further light on the processes of luminogenesis, deepening our understanding of the early formation of PDAC precancerous lesions, including cystic neoplasia.
在健康的外分泌胰腺中，管腔是组织结构的关键特征，在那里导管将酶从腺泡输送到肠道；在高致死性胰腺导管腺癌（PDAC）的癌前病变中，同样存在管腔，这些管腔可进一步发展成囊状结构。源自胰腺癌的分支类器官捕捉到了健康胰腺和患病胰腺的关键结构特征，包括管腔。然而，它们从实心细胞团向中空组织的转变仍未得到充分研究。在这里，我们表明类器官展示出两种正交但互补的管腔形成机制：一种依赖于液体摄入以进行多个微管腔的成核、肿胀和融合，另一种涉及中央细胞群的死亡，从而形成空洞。这些结果进一步揭示了管腔形成的过程，加深了我们对PDAC癌前病变早期形成过程的理解，包括囊性肿瘤形成。
