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Identification of t...
Identification of tissue-specific cell death using methylation patterns of circulating DNA
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- Lehmann-Werman, Roni (author)
- Hebrew Univ Jerusalem, Hadassah Med Sch, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, IL-91120 Jerusalem, Israel.
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- Neiman, Daniel (author)
- Hebrew Univ Jerusalem, Hadassah Med Sch, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, IL-91120 Jerusalem, Israel.
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- Zemmour, Hai (author)
- Hebrew Univ Jerusalem, Hadassah Med Sch, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, IL-91120 Jerusalem, Israel.
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- Moss, Joshua (author)
- Hebrew Univ Jerusalem, Hadassah Med Sch, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, IL-91120 Jerusalem, Israel.
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- Magenheim, Judith (author)
- Hebrew Univ Jerusalem, Hadassah Med Sch, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, IL-91120 Jerusalem, Israel.
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- Vaknin-Dembinsky, Adi (author)
- Hadassah Hebrew Univ, Med Ctr, Dept Neurol, IL-91120 Jerusalem, Israel.
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- Rubertsson, Sten (author)
- Uppsala universitet,Anestesiologi och intensivvård
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- Nellgård, Bengt, 1956 (author)
- Sahlgrens Univ Hosp, S-43180 Molndal, Sweden.
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- Blennow, Kaj, 1958 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Zetterberg, Henrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Spalding, Kirsty (author)
- Karolinska Institutet
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- Haller, Michael J. (author)
- Univ Florida, Coll Med, Div Endocrinol, Gainesville, FL 32610 USA.
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- Wasserfall, Clive H. (author)
- Univ Florida, Coll Med, Div Endocrinol, Gainesville, FL 32610 USA.
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- Schatz, Desmond A. (author)
- Univ Florida, Coll Med, Div Endocrinol, Gainesville, FL 32610 USA.
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- Greenbaum, Carla J. (author)
- Benaroya Res Inst, Seattle, WA 98101 USA.
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- Dorrell, Craig (author)
- Oregon Hlth & Sci Univ, Pape Family Pediat Res Inst, Portland, OR 97239 USA.
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- Grompe, Markus (author)
- Oregon Hlth & Sci Univ, Pape Family Pediat Res Inst, Portland, OR 97239 USA.
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- Zick, Aviad (author)
- Hadassah Hebrew Univ, Med Ctr, Dept Oncol, IL-91120 Jerusalem, Israel.
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- Hubert, Ayala (author)
- Hadassah Hebrew Univ, Med Ctr, Dept Oncol, IL-91120 Jerusalem, Israel.
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- Maoz, Myriam (author)
- Hadassah Hebrew Univ, Med Ctr, Dept Oncol, IL-91120 Jerusalem, Israel.
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- Fendrich, Volker (author)
- Univ Marburg, Dept Surg, D-35037 Marburg, Germany.
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- Bartsch, Detlef K. (author)
- Univ Marburg, Dept Surg, D-35037 Marburg, Germany.
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- Golan, Talia (author)
- Chaim Sheba Med Ctr, Dept Oncol, IL-52621 Tel Hashomer, Israel.
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- Ben Sasson, Shmuel A. (author)
- Hebrew Univ Jerusalem, Hadassah Med Sch, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, IL-91120 Jerusalem, Israel.
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- Zamir, Gideon (author)
- Hadassah Hebrew Univ, Med Ctr, Dept Expt Surg, IL-91120 Jerusalem, Israel.
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- Razin, Aharon (author)
- Hebrew Univ Jerusalem, Hadassah Med Sch, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, IL-91120 Jerusalem, Israel.
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- Cedar, Howard (author)
- Hebrew Univ Jerusalem, Hadassah Med Sch, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, IL-91120 Jerusalem, Israel.
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- Shapiro, A. M. James (author)
- Univ Alberta, Dept Surg, Edmonton, AB T6G 2R3, Canada.;Univ Alberta, Clin Islet Transplant Program, Edmonton, AB T6G 2R3, Canada.
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- Glaser, Benjamin (author)
- Hadassah Hebrew Univ, Med Ctr, Endocrinol & Metab Serv, IL-91120 Jerusalem, Israel.
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- Shemer, Ruth (author)
- Hebrew Univ Jerusalem, Hadassah Med Sch, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, IL-91120 Jerusalem, Israel.
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- Dor, Yuval (author)
- Hebrew Univ Jerusalem, Hadassah Med Sch, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, IL-91120 Jerusalem, Israel.
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Hebrew Univ Jerusalem, Hadassah Med Sch, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, IL-91120 Jerusalem, Israel Hadassah Hebrew Univ, Med Ctr, Dept Neurol, IL-91120 Jerusalem, Israel. (creator_code:org_t)
- 2016-03-14
- 2016
- English.
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:13, s. E1826-E1834
- Related links:
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https://www.pnas.org...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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 beta-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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- circulating DNA
- diagnosis
- methylation
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Lehmann-Werman, ...
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Neiman, Daniel
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Zemmour, Hai
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Moss, Joshua
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Magenheim, Judit ...
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Vaknin-Dembinsky ...
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show more...
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Rubertsson, Sten
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Nellgård, Bengt, ...
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Blennow, Kaj, 19 ...
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Zetterberg, Henr ...
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Spalding, Kirsty
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Haller, Michael ...
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Wasserfall, Cliv ...
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Schatz, Desmond ...
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Greenbaum, Carla ...
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Dorrell, Craig
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Grompe, Markus
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Zick, Aviad
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Hubert, Ayala
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Maoz, Myriam
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Fendrich, Volker
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Bartsch, Detlef ...
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Golan, Talia
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Ben Sasson, Shmu ...
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Zamir, Gideon
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Razin, Aharon
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Cedar, Howard
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Shapiro, A. M. J ...
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Glaser, Benjamin
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Shemer, Ruth
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Dor, Yuval
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Proceedings of t ...
- By the university
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Uppsala University
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Karolinska Institutet
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University of Gothenburg