小柯机器人

研究揭示具有模拟组织再生和癌症特征的膀胱类组装体
2020-12-17 14:57

韩国浦项科技大学Kunyoo Shin和首尔国立大学医院Ja Hyeon Ku研究组合作,揭示了具有模拟组织再生和癌症特征的膀胱类组装体。该项研究成果在线发表在2020年12月16日出版的《自然》杂志上。

研究人员通过将具有基质成分的组织干细胞重构生成了多层膀胱“类组装体”,以代表组织化的架构,其中上皮围绕基质和外层肌肉。这些类组装体在单细胞转录组水平上表现出成熟成年膀胱细胞的组成和基因表达特征,并具有对损伤再生反应的体内组织动力学。研究还开发了与恶性肿瘤对应的类组织体,以揭示尿路上皮癌的体内病理生理特征。

使用基因操纵的肿瘤-装配体平台,研究人员发现由基质骨形态发生蛋白(BMP)诱导的肿瘤因子FOXA1是诱导增强子重编程从而决定肿瘤表型的主要先驱因子,这提示了肿瘤和基质之间的FOXA1-BMP-hedgehog反馈轴在调控肿瘤可塑性过程中的重要功能。

据介绍,当前的类器官模型由于无法模仿成熟的器官结构和相关的组织微环境而受到限制。

附:英文原文

Title: Creation of bladder assembloids mimicking tissue regeneration and cancer

Author: Eunjee Kim, Seoyoung Choi, Byunghee Kang, JungHo Kong, Yubin Kim, Woong Hee Yoon, Hwa-Rim Lee, SungEun Kim, Hyo-Min Kim, HyeSun Lee, Chorong Yang, You Jeong Lee, Minyong Kang, Tae-Young Roh, Sungjune Jung, Sanguk Kim, Ja Hyeon Ku, Kunyoo Shin

Issue&Volume: 2020-12-16

Abstract: Current organoid models are limited by their inability to mimic mature organ architecture and associated tissue microenvironments1,2. Here we create multilayer bladder ‘assembloids’ by reconstituting tissue stem cells with stromal components to represent an organized architecture with an epithelium surrounding stroma and an outer muscle layer. These assembloids exhibit characteristics of mature adult bladders in cell composition and gene expression at the single-cell transcriptome level, and recapitulate in vivo tissue dynamics of regenerative responses to injury. We also develop malignant counterpart tumour assembloids to recapitulate the in vivo pathophysiological features of urothelial carcinoma. Using the genetically manipulated tumour-assembloid platform, we identify tumoural FOXA1, induced by stromal bone morphogenetic protein (BMP), as a master pioneer factor that drives enhancer reprogramming for the determination of tumour phenotype, suggesting the importance of the FOXA1–BMP–hedgehog signalling feedback axis between tumour and stroma in the control of tumour plasticity.

DOI: 10.1038/s41586-020-3034-x

Source: https://www.nature.com/articles/s41586-020-3034-x

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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