Methylome of human senescent hematopoietic progenitors
Abstract Senescence, a state of permanent cell cycle arrest, can be induced by DNA damage. This process, which was initially described in fibroblasts, is now recognized to occur in stem cells. It has been well characterized in cell lines, but there is currently very limited data available on human s...
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doaj-c6036cf5f6bb43ceaf9ddc995fe847042020-11-25T01:30:23ZengBMCExperimental Hematology & Oncology2162-36192018-12-01711710.1186/s40164-018-0123-8Methylome of human senescent hematopoietic progenitorsStephen Capone0Anthony R. Colombo1Benjamin K. Johnson2Tim J. Triche3Giridharan Ramsingh4Jane Anne Nohl Division of Hematology and Center for the Study of Blood Diseases, Keck School of Medicine of University of Southern CaliforniaJane Anne Nohl Division of Hematology and Center for the Study of Blood Diseases, Keck School of Medicine of University of Southern CaliforniaCenter for Epigenetics, Van Andel Research InstituteCenter for Epigenetics, Van Andel Research InstituteJane Anne Nohl Division of Hematology and Center for the Study of Blood Diseases, Keck School of Medicine of University of Southern CaliforniaAbstract Senescence, a state of permanent cell cycle arrest, can be induced by DNA damage. This process, which was initially described in fibroblasts, is now recognized to occur in stem cells. It has been well characterized in cell lines, but there is currently very limited data available on human senescence in vivo. We recently reported that the expression of transposable elements (TE), including endogenous retroviruses, was up-regulated along with inflammatory genes in human senescent hematopoietic stem and progenitor cells (HSPCs) in vivo. The mechanism of regulation of TE expression is not completely understood, but changes in DNA methylation and chromatin modifications are known to alter their expression. In order to elucidate the molecular mechanisms for TE up-regulation after senescence of HSPCs, we employed whole-genome bisulfite sequencing in paired senescent and active human HSPCs in vivo from healthy subjects. We found that the senescent HSPCs exhibited hypomethylated regions in the genome, which were enriched for TEs. This is the first report characterizing the methylome of senescent human HSPCs.http://link.springer.com/article/10.1186/s40164-018-0123-8SenescenceHematopoietic stem and progenitor cellsInflammationTransposable elementsEndogenous retrovirusesWhole genome bisulfite sequencing |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Stephen Capone Anthony R. Colombo Benjamin K. Johnson Tim J. Triche Giridharan Ramsingh |
spellingShingle |
Stephen Capone Anthony R. Colombo Benjamin K. Johnson Tim J. Triche Giridharan Ramsingh Methylome of human senescent hematopoietic progenitors Experimental Hematology & Oncology Senescence Hematopoietic stem and progenitor cells Inflammation Transposable elements Endogenous retroviruses Whole genome bisulfite sequencing |
author_facet |
Stephen Capone Anthony R. Colombo Benjamin K. Johnson Tim J. Triche Giridharan Ramsingh |
author_sort |
Stephen Capone |
title |
Methylome of human senescent hematopoietic progenitors |
title_short |
Methylome of human senescent hematopoietic progenitors |
title_full |
Methylome of human senescent hematopoietic progenitors |
title_fullStr |
Methylome of human senescent hematopoietic progenitors |
title_full_unstemmed |
Methylome of human senescent hematopoietic progenitors |
title_sort |
methylome of human senescent hematopoietic progenitors |
publisher |
BMC |
series |
Experimental Hematology & Oncology |
issn |
2162-3619 |
publishDate |
2018-12-01 |
description |
Abstract Senescence, a state of permanent cell cycle arrest, can be induced by DNA damage. This process, which was initially described in fibroblasts, is now recognized to occur in stem cells. It has been well characterized in cell lines, but there is currently very limited data available on human senescence in vivo. We recently reported that the expression of transposable elements (TE), including endogenous retroviruses, was up-regulated along with inflammatory genes in human senescent hematopoietic stem and progenitor cells (HSPCs) in vivo. The mechanism of regulation of TE expression is not completely understood, but changes in DNA methylation and chromatin modifications are known to alter their expression. In order to elucidate the molecular mechanisms for TE up-regulation after senescence of HSPCs, we employed whole-genome bisulfite sequencing in paired senescent and active human HSPCs in vivo from healthy subjects. We found that the senescent HSPCs exhibited hypomethylated regions in the genome, which were enriched for TEs. This is the first report characterizing the methylome of senescent human HSPCs. |
topic |
Senescence Hematopoietic stem and progenitor cells Inflammation Transposable elements Endogenous retroviruses Whole genome bisulfite sequencing |
url |
http://link.springer.com/article/10.1186/s40164-018-0123-8 |
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