Skip to main content

Table 1 A summary of scRNA-seq and ST-seq applied in liver research

From: ScRNA-seq and ST-seq in liver research

Classification

Methods

Major Findings

Reference

Liver development

scRNA-seq

Hepatobiliary hybrid progenitor (HHyP) cells at the ductal plate were found in human fetal liver, which own a hybrid transcriptome of both hepatic and biliary lineage.

Segal et al. 2019

scRNA-seq

ST-seq

A comprehensive map of primitive liver cell lineage was generated from the endoderm and mesoderm.

Lotto et al. 2020

scRNA-seq

The whole transcriptome of murine liver was sequenced and analyzed.

Halpern et al. 2017)

ST-seq

Spatial heterogeneity in each liver lobule shaped by differential transcriptomes along gradient was confirmed.

Hildebrandt et al. 2021

Spatial cell sorting

scRNA-seq

proteomics

/phosphoproteomics

Tyrosine phosphorylation is a unique zonated process and Tie1 phosphorylation acts specifically around central vein area as a signature of LSECs located around central vein.

Inverso et al. 2021

scRNA-seq

Various previously unknown subpopulations of LSECs, KCs and hepatocytes were found. Moreover, a TROP2int progenitor population was suggested.

Aizarani et al. 2019

scRNA-seq

Two subpopulations of HSCs were found. One population mainly produce collagen and are associated with liver fibrosis.

Dobie et al. 2019

scRNA-seq

Two subpopulations of KCs (a major CD206loESAM-population (KC1) and a minor CD206hiESAM+ population (KC2)) were suggested.

Blériot et al. 2021

scCITE-seq

3D reconstruction

This study suggested that there is only one population of KCs and the second population of KCs in previous study might be LSECs/KCs doublets.

Guilliams et al. 2022

ST-seq

ATAC-seq

ZNRF3 and RNF43 fine-tune activity of Wnt signaling-mediated proliferation in Axin2+ hepatocytes, thereby prevent hepatocytes proliferation but maintain metabolic zonation. This study suggested that Axin2+ hepatocytes are not likely hepatocyte progenitor cells.

Sun et al. 2021

Liver regeneration

scRNA-seq

bulk RNA-seq

ST-seq

Hepatocytes throughout the lobule proliferate almost equally to generate missing cells under mitotic pressure. Along this process, NPCs serve as zone-specific cues to instruct regeneration.

Ben-Moshe et al. 2022

scRNA-seq

A TROP2int progenitor population from normal human liver tissue was identified, which have a potential to form liver organoid in vitro.

Aizarani et al. 2019

scRNA-seq

LSECs contribute to hepatocytes regeneration via a Tie2/Wnt signaling pathway.

Inverso et al. 2021)

Seq-Scope

Spatial single-cell analysis of hepatocytes confirmed hepatocyte zonation and NPCs patial distribution was identified. Antioxidant genes in murine liver with early onset liver failure display zonated periportal-expression profile. With dead hepatocytes as the center, inflammatory macrophages and hep_injured cells are arranged around the periphery in turn.

Cho et al. 2021

scRNA-seq

Mice with acute liver injury present with new subpopulations of HSCs, LSECs, KCs, monocytes, neutrophils, and acute liver injury can be alleviated by inhibition of MYC.

Kolodziejczyk et al. 2020

Liver disease

ST-seq

Two populations of fibroblasts (Sparcl1+ population and Gja4+ population) were indicated. Sparcl1+ population is associated with reduced vascular invasion and increased patient survival.

Wang et al., 2021

scCITE-seq

sn-seq

ST-seq

A spatial proteogenomic atlas of the healthy and obese human and murine liver was generated. A population of lipid-associated macrophages (LAMs) at the bile ducts were identified, which was induced by local lipid exposure in steatotic liver. The development of KCs is dependent on their interaction with HSCs through the evolutionarily conservative ALK1-BMP9/10 axis.

(Guilliams et al. 2022

ST-seq

scRNA-seq

Tumor capsule prevents the infiltration of immune cells and thus redistributes immune cells around cancer. Moreover, tumor capsule affects intratumor spatial cluster continuity and transcriptome diversity.

(Wu et al., 2021

scRNA-seq

Region-specific changes of LSECs in liver cirrhosis were indicated. Genes associated with capillarization of LSECs and extracellular matrix are mostly upregulated in LSECs of Zone 3. In addition, LSECs of Zone 3 also showed a decrease expression of endocytic receptor in cirrhotic mice. NO production-related transcription factors such as Klf2, Klf4 and AP-1 are down-regulated in LSECs of all zones in cirrhotic mice, indicating increased intrahepatic vascular resistance.

(Su et al. 2021