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小鼠的单细胞转录学揭示了病的潜在细胞标
Jihwan Park1, Rojesh Shrestha1, Chengxiang Qiu1
1Renal Electrolyte and Hypertension Division, Department of Medicine and Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA.
概括
小鼠的单细胞RNA测序揭示了遗传性病的细胞类型起源. 收集管中的新发现的过渡细胞影响细胞命运,并且与病中的代谢性酸性病有关.
科学领域:
- 肝脏病学
- 分子生物学
- 遗传学
背景情况:
- 由于对细胞类型的分子表征有限,因此对病的发病原因的了解很少.
- 识别参与平衡的细胞类型对于了解疾病机制至关重要.
研究的目的:
- 使用单细胞RNA测序对健康小鼠中的细胞类型进行分子鉴定.
- 研究遗传性病的细胞起源,并确定功能和疾病中的新型细胞类型和途径.
主要方法:
- 来自健康小鼠脏的57,979个单细胞RNA测序.
- 计算细胞轨迹分析和体内血统追踪.
主要成果:
- 基因表达模式表明,脏疾病具有相似的表型,但具有不同的突变.
- 成年小鼠收集管中的新型过渡细胞产生多种细胞类型.
- 由Notch信号介导的间歇性和主要细胞转换,转移到病的主要细胞命运,与代谢酸性相关.
结论:
- 这项研究提供了健康小鼠的综合单细胞图谱,揭示了疾病的细胞类型特异性起源.
- 一个新发现的过渡细胞和Notch信号通路是收集管道中细胞命运的关键调节者.
- 病中细胞命运转变与代谢酸性有关,提供潜在的治疗点.
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