DNA Methylation Dynamics during In Vivo Differentiation of Blood and Skin Stem Cells

被引：301

作者：

Bock, Christoph ^{[2
,3
,4
]}

Beerman, Isabel ^{[3
,4
,5
]}

Lien, Wen-Hui ^{[1
]}

Smith, Zachary D. ^{[2
,3
,4
]}

Gu, Hongcang ^{[2
]}

Boyle, Patrick ^{[2
]}

Gnirke, Andreas ^{[2
]}

Fuchs, Elaine ^{[1
]}

Rossi, Derrick J. ^{[3
,4
,5
]}

Meissner, Alexander ^{[2
,3
,4
]}

机构：

[1] Rockefeller Univ, Lab Mammalian Cell Biol & Dev, Howard Hughes Med Inst, New York, NY 10065 USA

[2] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[3] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[4] Harvard Stem Cell Inst, Cambridge, MA 02318 USA

[5] Boston Childrens Hosp, Program Cellular & Mol Med, Immune Dis Inst, Boston, MA 02116 USA

来源：

MOLECULAR CELL | 2012年 / 47卷 / 04期

关键词：

HEMATOPOIETIC STEM; LINEAGE COMMITMENT; EXPRESSION; PLURIPOTENT; METHYLOME; STATES; MAPS; HYPERMETHYLATION; MULTIPOTENCY; LMO2;

D O I：

10.1016/j.molcel.2012.06.019

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

DNA methylation is a mechanism of epigenetic regulation that is common to all vertebrates. Functional studies underscore its relevance for tissue homeostasis, but the global dynamics of DNA methylation during in vivo differentiation remain underexplored. Here we report high-resolution DNA methylation maps of adult stem cell differentiation in mouse, focusing on 19 purified cell populations of the blood and skin lineages. DNA methylation changes were locus specific and relatively modest in magnitude. They frequently overlapped with lineage-associated transcription factors and their binding sites, suggesting that DNA methylation may protect cells from aberrant transcription factor activation. DNA methylation and gene expression provided complementary information, and combining the two enabled us to infer the cellular differentiation hierarchy of the blood lineage directly from genome-scale data. In summary, these results demonstrate that in vivo differentiation of adult stem cells is associated with small but informative changes in the genomic distribution of DNA methylation.

引用

页码：633 / 647

页数：15

共 35 条

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Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential:: A revised road map for adult blood lineage commitment [J].