Centre for Stem Cell and Regenerative Medicine, King's College London, London SE1 9RT, United Kingdom.
Max Delbrück Center for Molecular Medicine (MDC), D-13125 Berlin, Germany.
Cold Spring Harb Perspect Biol. 2020 Jul 1;12(7):a035626. doi: 10.1101/cshperspect.a035626.
Direct lineage reprogramming of abundant and accessible cells into therapeutically useful cell types holds tremendous potential in regenerative medicine. To date, a number of different cell types have been generated by lineage reprogramming methods, including cells from the neural, cardiac, hepatic, and pancreatic lineages. The success of this strategy relies on developmental biology and the knowledge of cell-fate-defining transcriptional networks. Hepatocytes represent a prime target for β cell conversion for numerous reasons, including close developmental origin, accessibility, and regenerative potential. We present here an overview of pancreatic and hepatic development, with a particular focus on the mechanisms underlying the divergence between the two cell lineages. Additionally, we discuss to what extent this lineage relationship can be exploited in efforts to reprogram one cell type into the other and whether such an approach may provide a suitable strategy for regenerative therapies of diabetes.
直接将丰富且易得的细胞重编程为具有治疗用途的细胞类型，在再生医学中具有巨大的潜力。迄今为止，通过谱系重编程方法已经产生了许多不同的细胞类型，包括神经细胞、心肌细胞、肝细胞和胰腺细胞。该策略的成功依赖于发育生物学和细胞命运决定转录网络的知识。由于多种原因，肝细胞是β细胞转化的主要靶标，包括密切的发育起源、可及性和再生潜力。我们在此介绍胰腺和肝脏的发育概述，特别关注导致两个细胞谱系分化的机制。此外，我们还讨论了这种谱系关系在将一种细胞类型重编程为另一种细胞类型的努力中可以被利用到何种程度，以及这种方法是否可能为糖尿病的再生治疗提供一种合适的策略。
