Genome-wide promoter DNA methylation dynamics of human hematopoietic progenitor cells during differentiation and aging

被引：149

作者：

Bocker, Michael T. ^{[1
]}

Hellwig, Isabelle ^{[2
]}

Breiling, Achim ^{[1
]}

Eckstein, Volker ^{[2
]}

Ho, Anthony D. ^{[2
]}

Lyko, Frank ^{[1
]}

机构：

[1] Deutsch Krebsforschungszentrum, DKFZ ZMBH Alliance, Div Epigenet, D-69120 Heidelberg, Germany

[2] Heidelberg Univ, Med Ctr, Dept Hematol Oncol, Heidelberg, Germany

来源：

BLOOD | 2011年 / 117卷 / 19期

关键词：

TRANSCRIPTION FACTOR-BINDING; STEM-CELLS; CPG ISLANDS; CHROMATIN; PLURIPOTENT; GENE; EXPRESSION; REGULATOR; METHYLOME; TARGETS;

D O I：

10.1182/blood-2011-01-331926

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

DNA methylation plays an important role in the self-renewal of hematopoietic stem cells and in the commitment to the lymphoid or myeloid lineages. Using purified CD34(+) hematopoietic progenitor cells and differentiated myeloid cell populations from the same human samples, we obtained detailed methylation profiles at distinct stages of hematopoiesis. We identified a defined set of differentiation-related genes that are methylated in CD34(+) hematopoietic progenitor cells but show pronounced DNA hypomethylation in monocytes and in granulocytes. In addition, by comparing hematopoietic progenitor cells from umbilical cord blood to hematopoietic progenitor cells from peripheral blood of adult donors we were also able to analyze age-related methylation changes in CD34(+) cells. Interestingly, the methylation changes observed in older progenitor cells showed a bimodal pattern with hypomethylation of differentiation-associated genes and de novo methylation events resembling epigenetic mutations. Our results thus provide detailed insight into the methylation dynamics during differentiation and suggest that epigenetic changes contribute to hematopoietic progenitor cell aging. (Blood. 2011; 117(19): e182-e189)

引用

页码：E182 / E189

页数：8

共 50 条

[1] Stem cells and the aging hematopoietic system [J].

Beerman, Isabel ;

Maloney, William J. ;

Weissmann, Irving L. ;

Rossi, Derrick J. .

CURRENT OPINION IN IMMUNOLOGY, 2010, 22 (04) :500-506

[2] Genome-wide DNA methylation profiling using Infinium® assay [J].

Bibikova, Marina ;

Le, Jennie ;

Barnes, Bret ;

Saedinia-Melnyk, Shadi ;

Zhou, Lixin ;

Shen, Richard ;

Gunderson, Kevin L. .

EPIGENOMICS, 2009, 1 (01) :177-200

[3] Targets and dynamics of promoter DNA methylation during early mouse development [J].

Borgel, Julie ;

Guibert, Sylvain ;

Li, Yufeng ;

Chiba, Hatsune ;

Schuebeler, Dirk ;

Sasaki, Hiroyuki ;

Forne, Thierry ;

Weber, Michael .

NATURE GENETICS, 2010, 42 (12) :1093-U90

[4] DNA methylation pattern changes upon long-term culture and aging of human mesenchymal stromal cells [J].

Bork, Simone ;

Pfister, Stefan ;

Witt, Hendrik ;

Horn, Patrick ;

Korn, Bernhard ;

Ho, Anthony D. ;

Wagner, Wolfgang .

AGING CELL, 2010, 9 (01) :54-63

[5] A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells [J].

Bouchon, A ;

Hernández-Munain, C ;

Cella, M ;

Colonna, M .

JOURNAL OF EXPERIMENTAL MEDICINE, 2001, 194 (08) :1111-1122

[6] DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction [J].

Broeske, Ann-Marie ;

Vockentanz, Lena ;

Kharazi, Shabnam ;

Huska, Matthew R. ;

Mancini, Elena ;

Scheller, Marina ;

Kuhl, Christiane ;

Enns, Andreas ;

Prinz, Marco ;

Jaenisch, Rudolf ;

Nerlov, Claus ;

Leutz, Achim ;

Andrade-Navarro, Miguel A. ;

Jacobsen, Sten Eirik W. ;

Rosenbauer, Frank .

NATURE GENETICS, 2009, 41 (11) :1207-1215

[7] JASPAR, the open access database of transcription factor-binding profiles: new content and tools in the 2008 update [J].

Bryne, Jan Christian ;

Valen, Eivind ;

Tang, Man-Hung Eric ;

Marstrand, Troels ;

Winther, Ole ;

da Piedade, Isabelle ;

Krogh, Anders ;

Lenhard, Boris ;

Sandelin, Albin .

NUCLEIC ACIDS RESEARCH, 2008, 36 :D102-D106

[8] Genome-wide conserved consensus transcription factor binding motifs are hyper-methylated [J].

Choy, Mun-Kit ;

Movassagh, Mehregan ;

Goh, Hock-Guan ;

Bennett, Martin R. ;

Down, Thomas A. ;

Foo, Roger S. Y. .

BMC GENOMICS, 2010, 11

[9] Epigenetic control of embryonic stem cell fate [J].

Christophersen, Nicolaj Stroyer ;

Helin, Kristian .

JOURNAL OF EXPERIMENTAL MEDICINE, 2010, 207 (11) :2287-2295

[10] Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts [J].

Doi, Akiko ;

Park, In-Hyun ;

Wen, Bo ;

Murakami, Peter ;

Aryee, Martin J. ;

Irizarry, Rafael ;

Herb, Brian ;

Ladd-Acosta, Christine ;

Rho, Junsung ;

Loewer, Sabine ;

Miller, Justine ;

Schlaeger, Thorsten ;

Daley, George Q. ;

Feinberg, Andrew P. .

NATURE GENETICS, 2009, 41 (12) :1350-U123

← 1 2 3 4 5 →