相关实验视频
Updated: Jun 13, 2025

Generation of Human Kidney Tubuloids from Tissue and Urine
Published on: April 16, 2021
管状上皮细胞调节元件的变异介于人类功能中的大多数遗传差异
Gabriel B Loeb1,2, Pooja Kathail3, Richard W Shuai4
1Division of Nephrology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA. Gabriel.Loeb@ucsf.edu.
这项研究确定了430个影响成年人功能的遗传区域. 这些对功能的遗传影响大多源于管表皮细胞和细胞细胞的变化.
科学领域:
- 遗传学 是一个遗传学.
- 腎臟病學 (nephrology) 是一種醫學專業.
- 基因组学就是基因组学.
背景情况:
- 功能衰竭显著影响发病率和死亡率.
- 了解功能遗传基础对于开发有效治疗方法至关重要.
研究的目的:
- 为了确定与功能相关的遗传位置.
- 确定功能遗传性中涉及的细胞类型和调控元素.
主要方法:
- 全基因组关联研究 (GWAS) 涉及406,504名英国生物库参与者.
- 将GWAS数据与人类脏中转化酶可访问的染色体测序 (scATAC-seq) 的单细胞测定集成.
- 增强剂测试,基因特异性scATAC-seq,机器学习和CRISPR干扰 (CRISPRi) 用于功能验证.
主要成果:
- 确定了430个与中年成人功能相关的位置.
- 56%的功能遗传局限于管内皮质候选 cis-regulatory元素 (cCREs),另有7%的 podocyte cCREs.
- 证明许多功能变异改变了管表皮细胞中的cCRE可访问性和功能,涉及NDRG1,CCNB1和STC1.1等基因.
结论:
- 成年人功能中的遗传性差异主要是由管内上皮细胞和细胞细胞中的基因表达改变所驱动的.
- 通过GWAS识别的遗传变异可以通过调节cCREs来对功能产生功能性影响.
- 这项研究为功能遗传结构提供了新的见解,并确定了潜在的治疗点.
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