小柯机器人

西湖大学Shang Cai团队的最新研究报道，体外重建的动态乳腺小腺体具有正常生理功能和肿瘤发生现象。相关论文于2023年11月2日发表在《自然-方法学》杂志上。

研究人员研发了一种长期成人干细胞衍生乳腺小腺体培养系统，该系统支持类器官稳健的三维外生长，再现了正常乳腺的形态、大小、细胞环境和转录异质性。细胞外基质、环境信号和动态生理周期的协调组合决定了干细胞的自组织能力和增殖稳定性。研究表明，这些微型腺体对激素有反应，能再现产后乳腺的发育过程，包括青春期、发情周期、哺乳期和内缩期。研究人员还观察到，这些微型腺体具有乳腺干细胞，并能在系谱追踪实验中重现从胚胎时双能性到产后单能性的命运转变。

此外，在诱导微型腺体表达癌基因后，研究人员在小鼠模型中观察到体外和体肿瘤的产生。总之，该研究提供了一个可维持动态微型乳腺的实验系统，用于研究与生理相关的复杂生物过程。

据悉，类器官培养已广泛用于正常组织重建和疾病建模。然而，在同源条件下建立模拟活体结构、大小和功能的类器官仍具有挑战。

附：英文原文

Title: Reconstruction of dynamic mammary mini gland in vitro for normal physiology and oncogenesis

Author: Yuan, Lei, Xie, Shaofang, Bai, Huiru, Liu, Xiaoqin, Cai, Pei, Lu, Jing, Wang, Chunhui, Lin, Zuobao, Li, Shuying, Guo, Yajing, Cai, Shang

Issue&Volume: 2023-11-02

Abstract: Organoid culture has been extensively exploited for normal tissue reconstruction and disease modeling. However, it is still challenging to establish organoids that mimic in vivo-like architecture, size and function under homeostatic conditions. Here we describe the development of a long-term adult stem cell-derived mammary mini gland culture system that supports robust three-dimensional outgrowths recapitulating the morphology, scale, cellular context and transcriptional heterogeneity of the normal mammary gland. The self-organization ability of stem cells and the stability of the outgrowths were determined by a coordinated combination of extracellular matrix, environmental signals and dynamic physiological cycles. We show that these mini glands were hormone responsive and could recapitulate the entire postnatal mammary development including puberty, estrus cycle, lactation and involution. We also observed that these mini glands maintained the presence of mammary stem cells and could also recapitulate the fate transition from embryonic bipotency to postnatal unipotency in lineage tracing assays. In addition, upon induction of oncogene expression in the mini glands, we observed tumor initiation in vitro and in vivo in a mouse model. Together, this study provides an experimental system that can support a dynamic miniature mammary gland for the study of physiologically relevant, complex biological processes.

DOI: 10.1038/s41592-023-02039-y

Source: https://www.nature.com/articles/s41592-023-02039-y

Nature Methods：《自然—方法学》，创刊于2004年。隶属于施普林格·自然出版集团，最新IF：47.99
官方网址：https://www.nature.com/nmeth/
投稿链接：https://mts-nmeth.nature.com/cgi-bin/main.plex