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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Schatz, Desmond A. Greenbaum, Carla J. Cedar, Howard Spalding, Kirsty Maoz, Myriam Grompe, Markus Bartsch, Detlef K. Hubert, Ayala Haller, Michael J. Dorrell, Craig Dor, Yuval Neiman, Daniel Zick, Aviad Razin, Aharon Rubertsson, Sten Golan, Talia Zetterberg, Henrik Glaser, Benjamin Nellgård, Bengt Lehmann-werman, Roni Zemmour, Hai Wasserfall, Clive H. Magenheim, Judith Vaknin-dembinsky, Adi Shemer, Ruth Ben Sasson, Shmuel A. Blennow, Kaj Zamir, Gideon Shapiro, A. M. James Moss, Joshua Fendrich, Volker |
| Description | Author Affiliation: Lehmann-Werman R ( Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel); Neiman D ( Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel); Zemmour H ( Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel); Moss J ( Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel); Magenheim J ( Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel); Vaknin-Dembinsky A ( Department of Neurology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel); Rubertsson S ( Department of Surgical Sciences/Anesthesiology and Intensive Care, Uppsala University Hospital, SE-751 85 Uppsala, Sweden); Nellgård B ( Sahlgrenska University Hospital, S-431 80 Molndal, Sweden); Blennow K ( Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, S-431 80 Molndal, Sweden); Zetterberg H ( Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, S-431 80 Molndal, Sweden); Spalding K ( Department of Cell and Molecular Biology, Karolinska Institute, Stockholm 171-77, Sweden); Haller MJ ( Division of Endocrinology, University of Florida College of Medicine, Gainesville, FL 32610); Wasserfall CH ( Division of Endocrinology, University of Florida College of Medicine, Gainesville, FL 32610); Schatz DA ( Division of Endocrinology, University of Florida College of Medicine, Gainesville, FL 32610); Greenbaum CJ ( Benaroya Research Institute, Seattle, WA 98101); Dorrell C ( Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland OR 97239); Grompe M ( Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland OR 97239); Zick A ( Department of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel); Hubert A ( Department of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel); Maoz M ( Department of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel); Fendrich V ( Department of Surgery, Marburg University, 35037 Marburg, Germany); Bartsch DK ( Department of Surgery, Marburg University, 35037 Marburg, Germany); Golan T ( Department of Oncology, Chaim Sheba Medical Center, Tel Hashomer, Israel); Ben Sasson SA ( Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel); Zamir G ( Department of Experimental Surgery, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel); Razin A ( Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel); Cedar H ( Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel); Shapiro AM ( Department of Surgery and the Clinical Islet Transplant Program, University of Alberta, Edmonton, AB T6G 2R3, Canada); Glaser B ( Endocrinology and Metabolism Service, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel beng@cc.huji.ac.il shemer.ru@mail.huji.ac.il yuvald@ekmd.huji.ac.il.); Shemer R ( Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel); Dor Y ( Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel); |
| 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 ß-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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 13 |
| Volume Number | 113 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2016-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | DNA Methylation DNA Blood Insulin-Secreting Cells Pathology Oligodendroglia Adolescent Brain Ischemia Genetics Case-Control Studies Cell Death Child, Preschool Metabolism Diabetes Mellitus, Type 1 Genetic Markers Multiple Sclerosis, Relapsing-Remitting Organ Specificity Pancreatic Neoplasms Pancreatitis, Chronic Promoter Regions, Genetic Sensitivity And Specificity Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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