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Temporal Analyses of Postnatal Liver Development and Maturation by Single Cell Transcriptomics

ABSTRACT: Temporal Analyses of Postnatal Liver Development and Maturation by Single Cell Transcriptomics

PROVIDER: PRJNA721659 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14228560_1.fastq.gz	Fastqsanger.gz
	SRR14228560_2.fastq.gz	Fastqsanger.gz
	SRR14228561_1.fastq.gz	Fastqsanger.gz
	SRR14228561_2.fastq.gz	Fastqsanger.gz
	SRR14228562_1.fastq.gz	Fastqsanger.gz

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Temporal Analyses of Postnatal Liver Development and Maturation by Single Cell Transcriptomics

Project description:The liver is the largest metabolic organ in mammals to process most nutrients and cellular wastes, although its development and maturation in postnatal life is unclear. We performed single cell RNA-sequencing (scRNA-seq) analysis focusing on postnatal development and maturation of murine liver. A total of 52,834 single cell transcriptomes, collected from the newborn to adult livers, were analyzed. We observed dramatic changes in cellular compositions during liver postnatal development. We characterized the process of hepatocytes and sinusoidal endothelial cell zonation establishment at single cell resolution. Furthermore, trajectory and gene regulatory analyses showed development of circadian clock in early liver as well as response of several critical metabolic pathways in order to adapt to the abrupt environmental changes at birth and in the postnatal life. Finally, we identified a special type of macrophages, enriched at postnatal day 7, with hybrid phenotype of both macrophage and endothelial cells. Cell-cell interaction analysis indicated this group of cells involved in regulation of liver sinusoidal vascularization and Treg cell activity. This study provides a comprehensive blueprint for further dissection of liver functions and diseases.

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Temporal analyses of postnatal liver development and maturation by single-cell transcriptomics.

Project description:The postnatal development and maturation of the liver, the major metabolic organ, are inadequately understood. We have analyzed 52,834 single-cell transcriptomes and identified 31 cell types or states in mouse livers at postnatal days 1, 3, 7, 21, and 56. We observe unexpectedly high levels of hepatocyte heterogeneity in the developing liver and the progressive construction of the zonated metabolic functions from pericentral to periportal hepatocytes, which is orchestrated with the development of sinusoid endothelial, stellate, and Kupffer cells. Trajectory and gene regulatory analyses capture 36 transcription factors, including a circadian regulator, Bhlhe40, in programming liver development. Remarkably, we identified a special group of macrophages enriched at day 7 with a hybrid phenotype of macrophages and endothelial cells, which may regulate sinusoidal construction and Treg-cell function. This study provides a comprehensive atlas that covers all hepatic cell types and is instrumental for further dissection of liver development, metabolism, and disease.

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