Single-Cell Analysis of Liver Development Post-Birth

DownLoad

Summary

In their investigation into the postnatal maturation of the liver, researchers examined 52,834 single-cell transcriptomes from mouse livers across various postnatal days, identifying 31 distinct cell types or states. The study unveiled a surprising level of heterogeneity among hepatocytes during liver development and outlined the step-by-step formation of zonated metabolic functions. This development synchronized with the maturation of other liver cells such as sinusoid endothelial and stellate cells. A set of 36 transcription factors, including Bhlhe40, played a pivotal role in directing liver growth. Notably, a unique macrophage group was discovered on day 7, showcasing attributes of both macrophages and endothelial cells, potentially influencing sinusoidal formation and Treg-cell operations. This research offers a valuable resource for deeper exploration of liver growth, metabolism, and related disorders.

Fig.1 Graphical abstract¹.

Research Criteria

The study aimed to understand the postnatal development and maturation of the liver, a major metabolic organ. The researchers 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. They observed hepatocyte heterogeneity in the developing liver and the progressive construction of zonated metabolic functions from pericentral to periportal hepatocytes.

Sample Type

The samples used for the single-cell experiments were mouse livers taken at postnatal days 1, 3, 7, 21, and 56.

Result—scRNA-Seq Shows Different Hepatocyte Subpopulations in the Early Postnatal Liver

In this study, researchers have meticulously charted the development of liver cells in mice from birth to adulthood using single-cell RNA sequencing (scRNA-seq). They successfully isolated and analyzed over 52,000 cells, identifying 31 distinct cell types or states. Remarkably, they discovered three unique groups of hepatocytes (liver cells) at different developmental stages. Early-stage hepatocytes (D1-D7) were found to be actively proliferating and not fully mature, while those from D21 were in a transitional phase. The study also revealed distinct subpopulations within hepatocytes at each time point, characterized by specific gene expressions. For instance, early-stage hepatocytes expressed genes linked to protein translation and metabolism, while later stages showed markers related to nuclear long non-coding RNAs (lncRNAs) and other functions. The research also highlighted the dynamic expression of Scd1 and Scd2, enzymes crucial for fatty acid biosynthesis, across different stages and cell types. This comprehensive analysis provides valuable insights into liver development and the intricate cellular changes that occur from neonatal stages to adulthood.

Fig.2 The scRNA-seq technique reveals hepatic cell types in the developing and adult liver¹.

Result—Maturation of Endothelial and Mesenchymal cell in the Liver

Liver endothelial cells (ECs) comprise macrovascular endothelial cells, lymphatic cells, and liver sinusoid endothelial cells (LSECs). While mature LSECs form two distinct groups, premature LSECs display higher heterogeneity without clear zonation. A developmental trajectory was constructed, tracing from embryonic stages to neonatal endothelial cells, highlighting the differentiation paths of these cells. Additionally, mesenchymal cells, known to be precursors to myofibroblasts post-liver injury, are categorized into hepatocellular stellate cells (HSCs), fibroblasts, and mesothelial cells, each with distinct markers and developmental paths.

Fig.3 Endothelial and mesenchymal cell development in the liver¹.

Creative Biolabs' Services

Single Cell RNA Sequencing Service

At Creative Biolabs, we harness our profound grasp of cellular diversity and asynchrony to present an expertly crafted range of services. Our proficiency encompasses sample readiness, blueprint creation, and in-depth data scrutiny, all fine-tuned to decode the detailed panorama of transcriptome variations in multifaceted samples. Through our holistic strategy, we infuse your project with unparalleled flexibility and fast-track its path to peak data accuracy.

Learn more

At Creative Biolabs, we pride ourselves on offering unparalleled single-cell RNA sequencing services to the global research community. Using cutting-edge tools and our deep knowledge, we generate precise scRNA-seq insights, revealing intricate genetic details within cells. We customize our offerings, ensuring they align with our clients' specific needs and financial boundaries. Our unwavering commitment positions us at the forefront of propelling scientific innovation.

For any information, please contact us.

Reference

1. Liang, Yan, et al. "Temporal analyses of postnatal liver development and maturation by single-cell transcriptomics." Developmental Cell 57.3 (2022): 398-414.