TUM München, Arcisstraße 21, 80333, Munich, Germany.
, Munich, Germany.
Cancer Metastasis Rev. 2020 Sep;39(3):953-958. doi: 10.1007/s10555-020-09897-4.
In the past years, a multitude of studies has been published in the field of pancreatic organogenesis to interrogate the critical regulators of endocrine lineage segregation. Preliminary, transcription factors are guiding the transcriptional hierarchy of the endocrine specified cells, underpinning the importance of open chromatin formation. Signaling pathways either inhibit or accelerate the transcriptional landscape of pancreatic organogenesis. Thus, the fine-tuned process in the former pancreatic multipotent progenitors in the mechanism of lineage segregation needs to be elucidated more precisely for unraveling the temporal-spatial lineage-determining factors.Previously, Willmann et al. described candidate gene regulators of lineage segregation during the secondary transition of pancreatic organogenesis. At embryonic stage (E) 12.5, the former multipotent pancreatic progenitor compartmentalizes into the acinar, ductal, and endocrine lineage. In the adult pancreatic gland, acinar cells secrete enzymes that are transported by the duct to the duodenum. In contrast, the endocrine cells are clustered within the acinar tissue in the Islets of Langerhans. These Islets of Langerhans consist of a subset of α, δ, ε, and PP cells and β cells, and the function of the α and β cells is predominantly described by regulating glucose homeostasis, contrary, the function of the additional subtypes in the Islets of Langerhans remains still unclear and is rather pointing to a supportive role for the α and β cells.The essential wave of endocrine precursor cells emerges at E 14.5 out of the ductal cord-like structure in a process called epithelial-to-mesenchymal transition (EMT). This EMT is a reversible and incomplete process that includes significant intermedia states. As EMT is in focus in the field of cancer research, missense in endocrine lineage segregation is linking to a progression of pancreatic cancer, to be more precise in adenocarcinoma, e.g., meaning pancreatic ductal adenocarcinoma.Thus, the previous review will further accelerate the understanding of EMT about endocrine lineage segregation, respective pancreatic ductal adenocarcinoma, and introduces factors previously only known for either lineage segregation or related in cancer disease into a complete picture.
在过去的几年中，已经有大量的研究在胰腺器官发生领域中发表，以探究内分泌谱系分离的关键调节因子。初步研究表明，转录因子指导着内分泌细胞的转录层次，这是开放染色质形成的基础。信号通路要么抑制，要么加速胰腺器官发生的转录景观。因此，需要更精确地阐明前胰腺多能祖细胞中谱系分离的精细过程，以揭示时空谱系决定因素。之前，Willmann 等人描述了胰腺器官发生的次级转变过程中谱系分离的候选基因调节因子。在胚胎期（E）12.5 时，前多能胰腺祖细胞区分为腺泡、导管和内分泌谱系。在成年胰腺中，腺泡细胞分泌的酶通过导管运输到十二指肠。相比之下，内分泌细胞则在胰岛组织中聚集。这些胰岛由一组α、δ、ε和 PP 细胞和β细胞组成，α和β细胞的功能主要描述为调节血糖稳态，相反，胰岛中其他亚型的功能仍然不清楚，而是指向对α和β细胞的支持作用。内分泌前体细胞的关键波在 E14.5 时从导管样结构中出现，这一过程称为上皮-间质转化（EMT）。EMT 是一个可逆和不完全的过程，包括重要的中间状态。由于 EMT 是癌症研究领域的焦点，内分泌谱系分离中的错义突变与胰腺癌的进展有关，更确切地说是在腺癌中，例如，胰腺导管腺癌。因此，这篇综述将进一步加速对 EMT 关于内分泌谱系分离、各自的胰腺导管腺癌的理解，并将以前仅在谱系分离或癌症疾病中相关的因素引入到一个完整的图景中。
