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器官内单细胞CRISPR查揭示了肝细胞分化和成熟的决定因素

Junbo Liang¹, Jinsong Wei², Jun Cao^1,3

¹State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking, Union Medical College, Beijing, 100005, China.

|November 1, 2023

概括

我们开发了OSCAR,这是分析有机单细胞CRISPR屏幕的新框架. 通过分析转录因子活性,OSCAR确定了肝细胞分化的关键调节者,揭示了Fos和Ubr5作为关键因素.

科学领域:

干细胞生物学干细胞生物学
基因组学就是基因组学.
再生医学是一种再生医学.

背景情况:

了解肝细胞分化中的遗传因素对于研究和再生医学至关重要.
在有机体中单细胞CRISPR屏幕提供了一种强大的方法来研究细胞命运调节者.
从单细胞测序数据准确估计转录因子 (TF) 表达,由于噪音和低表达水平,这是一个挑战.

研究的目的:

开发一个新的框架,OSCAR,用于分析基因淘汰效应在有机体使用regular活动作为readouts.
使用这个新的框架,确定肝细胞分化和成熟的关键调节者.

主要方法:

基于器官的单细胞CRISPR查分析与规则 (OSCAR) 框架的开发.
应用OSCAR在成年干细胞衍生肝脏器官上,有246个干扰.
对80,576个单细胞进行转录组分析,以确定基因淘汰效应.

主要成果:

奥斯卡成功地确定了已知的和新的肝细胞形成调节者.
Fos和Ubr5被确定为排名最高的监管机构.
耗促进了肝细胞的分化,而Ubr5淘汰则延迟了肝脏器官的成熟.

结论:

奥斯卡提供了一个快速而系统的框架来探索血统特征.
该研究确定了具有潜在临床应用的关键肝细胞决定因素.

关键词:

肝细胞的分化和成熟.有机器人机器人机器人机器人在 Regulon Regulon 中使用.一个单细胞的CRISPR屏幕.

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CRISPR

CRISPR

Genome editing technologies allow scientists to modify an organism’s DNA via the addition, removal, or rearrangement of genetic material at specific genomic locations. These types of techniques could potentially be used to cure genetic disorders such as hemophilia and sickle cell anemia. One popular and widely used DNA-editing research tool that could lead to safe and effective cures for genetic disorders is the CRISPR-Cas9 system. CRISPR-Cas9 stands for Clustered Regularly Interspaced Short...

CRISPR

CRISPR

Genome editing technologies allow scientists to modify an organism’s DNA via the addition, removal, or rearrangement of genetic material at specific genomic locations. These types of techniques could potentially be used to cure genetic disorders such as hemophilia and sickle cell anemia. One popular and widely used DNA-editing research tool that could lead to safe and effective cures for genetic disorders is the CRISPR-Cas9 system. CRISPR-Cas9 stands for Clustered Regularly Interspaced Short...