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Circulating, cell-free methylated DNA reveals cellular sources of allograft injury after liver transplant

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE262275 | GEO | 2025/03/02

REPOSITORIES: GEO

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Circulating, cell-free methylated DNA reveals cellular sources of allograft injury after liver transplant (LTR cell-free DNA)

Project description:Molecular biomarkers to monitor changes after liver transplant are essential to reveal mechanisms of injury, guide clinical decision-making and improve patient outcomes. Current approaches have limited scope and are unable to differentiate between host and graft amongst the causes of graft injury. Here, we utilize circulating, cell-free methylated DNA released from dying cells to monitor cellular damages after liver transplant impacting the graft tissue as well as host organs. We expand existing cell-type-specific DNA methylation atlases curated from whole-genome bisulfite sequencing (WGBS) of healthy tissues to characterize liver cell-types relevant to injury progression and tissue repair. Liver cell-type-specific methylation blocks are validated through multi-omic data integration and found to be enriched in open chromatin and regulatory regions functionally important for the respective cell populations. Cell-free DNA (cfDNA) fragments were captured from patient serum by hybridization to CpG-rich DNA panels and mapped to the expanded DNA methylation atlases to inform tissue origins of cell types. We profiled 135 blood samples collected from 44 liver transplant patients at serial time points before and after transplant. We found that liver transplant initially results in multi-tissue cellular damage that subsequently recovers in patients with graft acceptance during the first post-operative week. Further, we show that sustained elevation of hepatocyte and biliary epithelial cfDNA beyond the first week is indicative of early-onset graft injury. Most notably, cfDNA composition can differentiate amongst causes of graft injury. Thus, cell-free methylated DNA can detect cellular damages and prompt early intervention.

2025-03-02 | GSE262273 | GEO

Circulating, cell-free methylated DNA reveals cellular sources of allograft injury after liver transplant [Reference Celltype Chromatin]

2025-03-02 | GSE263243 | GEO

Circulating, cell-free methylated DNA reveals cellular sources of allograft injury after liver transplant (LTR reference cell type)

2025-03-02 | GSE262274 | GEO

Circulating, cell-free methylated DNA reveals cellular sources of allograft injury after liver transplant

Project description:Circulating, cell-free methylated DNA reveals cellular sources of allograft injury after liver transplant

| PRJNA1100632 | ENA

Circulating, cell-free methylated DNA reveals cellular sources of allograft injury after liver transplant

Project description:Circulating, cell-free methylated DNA reveals cellular sources of allograft injury after liver transplant

| PRJNA1100631 | ENA

Circulating, cell-free methylated DNA reveals cellular sources of allograft injury after liver transplant

Project description:Circulating, cell-free methylated DNA reveals cellular sources of allograft injury after liver transplant

| PRJNA1090942 | ENA

Circulating, cell-free methylated DNA reveals cellular sources of allograft injury after liver transplant (LTR cell-free DNA)

Project description:Circulating, cell-free methylated DNA reveals cellular sources of allograft injury after liver transplant (LTR cell-free DNA)

| PRJNA1090946 | ENA

Circulating, cell-free methylated DNA reveals cellular sources of allograft injury after liver transplant [Reference Celltype Chromatin]

Project description:Circulating, cell-free methylated DNA reveals cellular sources of allograft injury after liver transplant [Reference Celltype Chromatin]

| PRJNA1096335 | ENA

Circulating, cell-free methylated DNA reveals cellular sources of allograft injury after liver transplant (LTR reference cell type)

Project description:Circulating, cell-free methylated DNA reveals cellular sources of allograft injury after liver transplant (LTR reference cell type)

| PRJNA1090947 | ENA

Circulating cell-free methylated DNA reveals tissue-specific, cellular damage from radiation treatment.

Project description:Radiation therapy is an effective cancer treatment, although damage to healthy tissues is common. Here we analyzed cell-free, methylated DNA released from dying cells into the circulation to evaluate radiation-induced cellular damage in different tissues. To map the circulating DNA fragments to human and mouse tissues, we established sequencing-based, cell-type-specific reference DNA methylation atlases. We found that cell-type-specific DNA blocks were mostly hypomethylated and located within signature genes of cellular identity. Cell-free DNA fragments were captured from serum samples by hybridization to CpG-rich DNA panels and mapped to the DNA methylation atlases. In a mouse model, thoracic radiation-induced tissue damage was reflected by dose-dependent increases in lung endothelial and cardiomyocyte methylated DNA in serum. The analysis of serum samples from patients with breast cancer undergoing radiation treatment revealed distinct dose-dependent and tissue-specific epithelial and endothelial responses to radiation across multiple organs. Strikingly, patients treated for right-sided breast cancers also showed increased hepatocyte and liver endothelial DNA in the circulation, indicating the impact on liver tissues. Thus, changes in cell-free methylated DNA can uncover cell-type-specific effects of radiation and provide a readout of the biologically effective radiation dose received by healthy tissues.

| S-EPMC10443812 | biostudies-literature

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