单细胞RNA-seq和ATAC-seq的综合分析揭示了诱导多能干细胞源性肝器官样体的异质性。
Integrative analysis of single-cell RNA-seq and ATAC-seq reveals heterogeneity of induced pluripotent stem cell-derived hepatic organoids.
发表日期：2023 Sep 15
作者：
Jong-Hwan Kim, Seon Ju Mun, Jeong-Hwan Kim, Myung Jin Son, Seon-Young Kim
来源：
Epigenetics & Chromatin
摘要：
为了对器官结节的转录组和表观遗传组获得更深入的见解，我们对两种状态的肝脏结节（可扩展和更加分化）进行了单细胞RNA测序（scRNA-seq）和单细胞ATAC测序（scATAC-seq）分析。在分化的肝细胞中，线粒体基因表达较非分化肝细胞更高，ATAC-seq峰值在线粒体控制区域周围增加。肝脏结节的分化导致转录因子表达的增强和抑制作为诱导剂。此外，调节胎儿结蛋白（AFP）和白蛋白（ALB）表达的表观遗传机制在肝脏结节和成人肝脏中有所不同。下调胰腺发育的必需转录因子PDX1通过调节AFP和ALB表达促进了肝脏结节的肝分化。这种对肝脏结节转录组和表观遗传组的细胞水平整合分析有助于更好地了解肝脏发育期间的调控网络，并进一步发展成熟的体外人体肝模型。© 2023 作者。
To gain deeper insights into transcriptomes and epigenomes of organoids, liver organoids from two states (expandable and more differentiated) were subjected to single-cell RNA-seq (scRNA-seq) and single-cell ATAC-seq (scATAC-seq) analyses. Mitochondrial gene expression was higher in differentiated than in non-differentiated hepatocytes, with ATAC-seq peaks increasing near the mitochondrial control region. Differentiation of liver organoids resulted in the expression of transcription factors that act as enhancers and repressors. In addition, epigenetic mechanisms regulating the expression of alpha-fetoprotein (AFP) and albumin (ALB) differed in liver organoids and adult liver. Knockdown of PDX1, an essential transcription factor for pancreas development, led to the hepatic maturation of liver organoids through regulation of AFP and ALB expression. This integrative analysis of the transcriptomes and epigenomes of liver organoids at the single-cell level may contribute to a better understanding of the regulatory networks during liver development and the further development of mature in vitro human liver models.© 2023 The Author(s).