相关实验视频

Updated: Jul 19, 2025

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors

Published on: August 5, 2022

与DNA甲基化相关的等位基因失活调节了胰腺发育和致癌过程中的克拉19基因表达

Jana Krüger¹, Anja Fischer², Markus Breunig¹

¹Institute of Molecular Oncology and Stem Cell Biology, Ulm University Hospital, Ulm, Germany.

The Journal of pathology

|August 9, 2023

概括

在胰腺管的发育过程中,蛋白19 (KRT19) 的表达从双基转变为单基. 在KRAS突变胰腺管腺癌 (PDAC) 中异常的KRT19再激活表明在恶性瘤和潜在生物标志物中发挥作用.

科学领域:

细胞生物学细胞生物学
发展生物学发展生物学
癌症生物学癌症生物学

背景情况:

蛋白19 (KRT19) 是胰腺管道血统和胰腺管道腺癌 (PDAC) 的关键标记物.
了解KRT19表达动态对于PDAC研究至关重要.

研究的目的:

研究胰腺发育期间KRT19表达的调节及其在PDAC中的异常表达.
建立基于人类多能干细胞 (PSC) 的报告系统,用于监测内源性KRT19表达.

主要方法:

在人类PSC中开发了一个KRT19-mCherry记者系统.
利用差异化协议产生类似胰腺管的有机体.
进行DNA甲基化分析,并用DNA-甲基转移酶抑制剂对待细胞.
分析了人类PDAC队列和单细胞转录组.
在患者血中测量了可溶性KRT19蛋白.

主要成果:

从早期的内皮阶段观察到KRT19/mCherry表达,在胰腺内皮和前体阶段几乎无处不在.
在管道成熟过程中,从双基转变为单基的KRT19表达发生.
在KRT19位点的DNA甲基化模式在成熟过程中发生了变化,这种转换在抑制剂时是部分可逆的.
瘤性KRAS^G12D信号在有机体和人类PDAC中重新激活双基KRT19表达.
高KRT19水平与低位甲基化和PDAC患者的生存率降低相关.
在血中溶解的KRT19显示了基于治疗方案的存活率的差异相关性.

结论:

在胰腺管道系的进入过程中,KRT19的表达通过切换到单基表达来严格调节.
在瘤性KRAS^G12D表达时异常双基KRT19的活性化突显了它在PDAC发育和恶性瘤中的作用.
可溶性KRT19可以作为分层PDAC治疗的有价值的生物标志物.

关键词:

通过DNA甲基化.KRT19 在线观看双合体双合体的双合体.基因表达的基因表达方式在体外分化的体外分化.一个单基单基.胰腺癌是一种癌症.胰腺发育胰腺发育胰腺有机物胰腺有机物多能干细胞是一种多能干细胞.

更多相关视频

Mimicking and Manipulating Pancreatic Acinar-to-Ductal Metaplasia in 3-dimensional Cell Culture

Mimicking and Manipulating Pancreatic Acinar-to-Ductal Metaplasia in 3-dimensional Cell Culture

Published on: February 11, 2019

Immunostaining for DNA Modifications: Computational Analysis of Confocal Images

Immunostaining for DNA Modifications: Computational Analysis of Confocal Images

Published on: September 7, 2017

相关概念视频

Epigenetic Regulation

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...

Abnormal Proliferation

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...

Genomic Imprinting and Inheritance

Genomic Imprinting and Inheritance

Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...

Loss of Tumor Suppressor Gene Functions

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...