生物
祖细胞
转录因子
细胞生物学
祖细胞
细胞命运测定
刺猬信号通路
胰腺
信号
癌症研究
信号转导
基因
干细胞
遗传学
内分泌学
作者
Sophie Escot,David Willnow,Heike Naumann,Silvia Di Francescantonio,Francesca M. Spagnoli
标识
DOI:10.1038/s41467-018-07474-6
摘要
A complex interplay of intrinsic factors and extrinsic signalling pathways controls both cell lineage commitment and maintenance of cell identity. Loss of defined cellular states is the cause of many different cancers, including pancreatic cancer. Recent findings suggest a clinical role for the conserved SLIT/ROBO signalling pathway in pancreatic cancer. However, whilst this pathway has been extensively studied in many processes, a role for Slit and Robo genes in pancreas cell identity and plasticity has not been established yet. Here, we identify Slit/Robo signalling as a key regulator of pancreatic progenitor identity. We find that Robo1 and Robo2 are required for preserving pancreatic cell identity shortly after fate induction and, subsequently, for expansion of the pancreatic progenitor pool in the mouse. Furthermore, we show that Robo receptors control the expression of Tead transcription factors as well as its downstream transcriptional activity. Our work identifies an interplay between Slit/Robo pathway and Tead intrinsic regulators, functioning as gatekeeper of pancreatic cell identity.
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