当前位置： SCI文献检索 > PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA期刊下所有文献 > Identification of tissue-specific cell death using methylation patterns of circulating DNA.

Identification of tissue-specific cell death using methylation patterns of circulating DNA.

Abstract：

:Minimally invasive detection of cell death could prove an invaluable resource in many physiologic and pathologic situations. Cell-free circulating DNA (cfDNA) released from dying cells is emerging as a diagnostic tool for monitoring cancer dynamics and graft failure. However, existing methods rely on differences in DNA sequences in source tissues, so that cell death cannot be identified in tissues with a normal genome. We developed a method of detecting tissue-specific cell death in humans based on tissue-specific methylation patterns in cfDNA. We interrogated tissue-specific methylome databases to identify cell type-specific DNA methylation signatures and developed a method to detect these signatures in mixed DNA samples. We isolated cfDNA from plasma or serum of donors, treated the cfDNA with bisulfite, PCR-amplified the cfDNA, and sequenced it to quantify cfDNA carrying the methylation markers of the cell type of interest. Pancreatic β-cell DNA was identified in the circulation of patients with recently diagnosed type-1 diabetes and islet-graft recipients; oligodendrocyte DNA was identified in patients with relapsing multiple sclerosis; neuronal/glial DNA was identified in patients after traumatic brain injury or cardiac arrest; and exocrine pancreas DNA was identified in patients with pancreatic cancer or pancreatitis. This proof-of-concept study demonstrates that the tissue origins of cfDNA and thus the rate of death of specific cell types can be determined in humans. The approach can be adapted to identify cfDNA derived from any cell type in the body, offering a minimally invasive window for diagnosing and monitoring a broad spectrum of human pathologies as well as providing a better understanding of normal tissue dynamics.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Lehmann-Werman R,Neiman D,Zemmour H,Moss J,Magenheim J,Vaknin-Dembinsky A,Rubertsson S,Nellgård B,Blennow K,Zetterberg H,Spalding K,Haller MJ,Wasserfall CH,Schatz DA,Greenbaum CJ,Dorrell C,Grompe M,Zick A,Hubert A,M

doi

10.1073/pnas.1519286113

subject

Has Abstract

pub_date

2016-03-29 00:00:00

pages

E1826-34

issue

eissn

0027-8424

issn

1091-6490

pii

1519286113

journal_volume

113

pub_type

杂志文章

在线工具

Identification of tissue-specific cell death using methylation patterns of circulating DNA.