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Identification of tissue-specific cell death using methylation patterns of circulating DNA
Roni Lehmann-Werman1, Daniel Neiman1, Hai Zemmour1
1Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel;
Summary
Detecting cell death is now possible using tissue-specific methylation patterns in cell-free DNA (cfDNA). This breakthrough allows for minimally invasive diagnosis and monitoring of various human diseases and tissue dynamics.
Area of Science:
- Biochemistry
- Genomics
- Molecular Biology
Background:
- Cell-free circulating DNA (cfDNA) is a promising biomarker for monitoring diseases like cancer and graft failure.
- Current cfDNA analysis methods are limited as they require sequence differences, hindering detection in normal tissues.
- A minimally invasive method for detecting cell death in specific tissues is needed.
Purpose of the Study:
- To develop a novel method for detecting tissue-specific cell death using cfDNA.
- To identify cell type-specific DNA methylation signatures for diagnostic purposes.
- To demonstrate the feasibility of this approach in various human pathologies.
Main Methods:
- Interrogated tissue-specific methylome databases to find cell type-specific DNA methylation signatures.
- Developed a method to detect these signatures in cfDNA isolated from plasma or serum.
- Utilized bisulfite treatment, PCR amplification, and sequencing to quantify cfDNA with specific methylation markers.
Main Results:
- Successfully identified pancreatic β-cell DNA in type-1 diabetes and islet-graft patients.
- Detected oligodendrocyte DNA in patients with multiple sclerosis.
- Identified neuronal/glial DNA post-brain injury/cardiac arrest and exocrine pancreas DNA in pancreatic diseases.
Conclusions:
- This study proves that the tissue origin of cfDNA can be determined in humans, enabling the assessment of specific cell death rates.
- The developed method offers a minimally invasive approach for diagnosing and monitoring a wide range of human pathologies.
- This technique provides a new window into understanding normal tissue dynamics and disease progression.
