Monocyte-derived macrophages orchestrate multiple cell-type interactions to repair necrotic liver lesions
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA954775 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24144052.fastq.gz | Fastqsanger.gz | |||
| SRR24144053.fastq.gz | Fastqsanger.gz | |||
| SRR24144054.fastq.gz | Fastqsanger.gz | |||
| SRR24144055.fastq.gz | Fastqsanger.gz | |||
| SRR24144056.fastq.gz | Fastqsanger.gz |
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Project description:The liver can fully regenerate after partial resection and its underlying mechanisms have been extensively studied. The liver can also rapidly regenerate after injury with most studies focusing on hepatocyte proliferation; however, how hepatic necrotic lesions during acute or chronic liver diseases are eliminated and repaired remains obscure. Here we demonstrate that monocyte-derived macrophages (MoMFs) are rapidly recruited to and encapsulate necrotic areas during immune-mediated liver injury, and this feature is essential in repairing necrotic lesions. At the early stage of injury, infiltrating MoMFs activate the JAG1-NOTCH2 axis to induce cell death-resistant SOX9+ hepatocytes near the necrotic lesions, which acts as a barrier from further injury. Subsequently, necrotic environment (hypoxia and dead cells) induces a cluster of C1q+MoMFs that promote necrotic removal and liver repair, while Pdgfb+MoMFs activate hepatic stellate cells (HSCs) to express a-smooth muscle actin and induce a strong contraction signal (YAP, pMLC) to squeeze and finally eliminate the necrotic lesions. In conclusion, MoMFs play a key role in repairing the necrotic lesions not only by removing necrotic tissues but also by inducing cell death resistant hepatocytes to form a perinecrotic capsule and by activating a-smooth actin expressing HSCs to facilitate necrotic lesion resolution.
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Project description:The liver can fully regenerate after partial resection, and its underlying mechanisms have been extensively studied. The liver can also rapidly regenerate after injury, with most studies focusing on hepatocyte proliferation; however, how hepatic necrotic lesions during acute or chronic liver diseases are eliminated and repaired remains obscure. Here, we demonstrate that monocyte-derived macrophages (MoMFs) were rapidly recruited to and encapsulated necrotic areas during immune-mediated liver injury and that this feature was essential in repairing necrotic lesions. At the early stage of injury, infiltrating MoMFs activated the Jagged1/notch homolog protein 2 (JAG1/NOTCH2) axis to induce cell death-resistant SRY-box transcription factor 9+ (SOX9+) hepatocytes near the necrotic lesions, which acted as a barrier from further injury. Subsequently, necrotic environment (hypoxia and dead cells) induced a cluster of complement 1q-positive (C1q+) MoMFs that promoted necrotic removal and liver repair, while Pdgfb+ MoMFs activated hepatic stellate cells (HSCs) to express α-smooth muscle actin and induce a strong contraction signal (YAP, pMLC) to squeeze and finally eliminate the necrotic lesions. In conclusion, MoMFs play a key role in repairing the necrotic lesions, not only by removing necrotic tissues, but also by inducing cell death-resistant hepatocytes to form a perinecrotic capsule and by activating α-smooth muscle actin-expressing HSCs to facilitate necrotic lesion resolution.
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