Frontiers in Molecular Neuroscience (Jul 2021)
Bisulfite Amplicon Sequencing Can Detect Glia and Neuron Cell-Free DNA in Blood Plasma
- Zac Chatterton,
- Zac Chatterton,
- Zac Chatterton,
- Zac Chatterton,
- Zac Chatterton,
- Natalia Mendelev,
- Natalia Mendelev,
- Natalia Mendelev,
- Natalia Mendelev,
- Sean Chen,
- Sean Chen,
- Sean Chen,
- Sean Chen,
- Walter Carr,
- Walter Carr,
- Gary H. Kamimori,
- Yongchao Ge,
- Andrew J. Dwork,
- Andrew J. Dwork,
- Andrew J. Dwork,
- Fatemeh Haghighi,
- Fatemeh Haghighi,
- Fatemeh Haghighi,
- Fatemeh Haghighi
Affiliations
- Zac Chatterton
- Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Zac Chatterton
- Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Zac Chatterton
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Zac Chatterton
- Medical Epigenetics, James J. Peters VA Medical Center, New York, NY, United States
- Zac Chatterton
- Brain and Mind Centre, School of Medical Science, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
- Natalia Mendelev
- Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Natalia Mendelev
- Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Natalia Mendelev
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Natalia Mendelev
- Medical Epigenetics, James J. Peters VA Medical Center, New York, NY, United States
- Sean Chen
- Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Sean Chen
- Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Sean Chen
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Sean Chen
- Medical Epigenetics, James J. Peters VA Medical Center, New York, NY, United States
- Walter Carr
- Walter Reed Army Institute of Research, Silver Spring, MD, United States
- Walter Carr
- Oak Ridge Institute for Science and Education, Oak Ridge, TN, United States
- Gary H. Kamimori
- Walter Reed Army Institute of Research, Silver Spring, MD, United States
- Yongchao Ge
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Andrew J. Dwork
- Department of Pathology and Cell Biology, Columbia University, New York, NY, United States
- Andrew J. Dwork
- Department of Psychiatry, Columbia University, New York, NY, United States
- Andrew J. Dwork
- 0Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, NY, United States
- Fatemeh Haghighi
- Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Fatemeh Haghighi
- Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Fatemeh Haghighi
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
- Fatemeh Haghighi
- Medical Epigenetics, James J. Peters VA Medical Center, New York, NY, United States
- DOI
- https://doi.org/10.3389/fnmol.2021.672614
- Journal volume & issue
-
Vol. 14
Abstract
Sampling the live brain is difficult and dangerous, and withdrawing cerebrospinal fluid is uncomfortable and frightening to the subject, so new sources of real-time analysis are constantly sought. Cell-free DNA (cfDNA) derived from glia and neurons offers the potential for wide-ranging neurological disease diagnosis and monitoring. However, new laboratory and bioinformatic strategies are needed. DNA methylation patterns on individual cfDNA fragments can be used to ascribe their cell-of-origin. Here we describe bisulfite sequencing assays and bioinformatic processing methods to identify cfDNA derived from glia and neurons. In proof-of-concept experiments, we describe the presence of both glia- and neuron-cfDNA in the blood plasma of human subjects following mild trauma. This detection of glia- and neuron-cfDNA represents a significant step forward in the translation of liquid biopsies for neurological diseases.
Keywords