Home LiteratureArticle Details
PMID: 22841485 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

DNA methylation dynamics during in vivo differentiation of blood and skin stem cells.

Molecular cell ·Vol. 47 ·No. 4 ·2012-08-24 ·Pages 633-47

Bock C, Beerman I, Lien WH, Smith ZD, Gu H, Boyle P, Gnirke A, Fuchs E, Rossi DJ, Meissner A

Abstract

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.

MeSH Terms
Adult Stem Cells/cytology Animals Binding Sites Blood Cells/cytology Cell Cycle/genetics Cell Differentiation/genetics Cell Lineage DNA Methylation Down-Regulation Epigenomics Gene Expression Genes, Homeobox/genetics Genetic Loci Genome/genetics Lymphocytes/cytology Mice Myeloid Cells/cytology Skin/cytology
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Bock Christoph
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Beerman Isabel
Lien Wen-Hui
Smith Zachary D
Gu Hongcang
Boyle Patrick
Gnirke Andreas
Fuchs Elaine
Rossi Derrick J
Meissner Alexander
References (35)
35 references, click to expand
  1. Inactivation of HOXA genes by hypermethylation in myeloid and lymphoid malignancy is frequent and associated with poor prognosis.
    Clin Cancer Res. 2007 Sep 1;13(17):5048-55 PMID: 17785556
  2. Genome-scale DNA methylation maps of pluripotent and differentiated cells.
    Nature. 2008 Aug 7;454(7205):766-70 PMID: 18600261
  3. Tcf3 and Tcf4 are essential for long-term homeostasis of skin epithelia.
    Nat Genet. 2009 Oct;41(10):1068-75 PMID: 19718027
  4. Ectopic retroviral expression of LMO2, but not IL2Rgamma, blocks human T-cell development from CD34+ cells: implications for leukemogenesis in gene therapy.
    Leukemia. 2007 Apr;21(4):754-63 PMID: 17268520
  5. Lineage-specific polycomb targets and de novo DNA methylation define restriction and potential of neuronal progenitors.
    Mol Cell. 2008 Jun 20;30(6):755-66 PMID: 18514006
  6. Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche.
    Cell. 2004 Sep 3;118(5):635-48 PMID: 15339667
  7. Directional DNA methylation changes and complex intermediate states accompany lineage specificity in the adult hematopoietic compartment.
    Mol Cell. 2011 Oct 7;44(1):17-28 PMID: 21924933
  8. Reference Maps of human ES and iPS cell variation enable high-throughput characterization of pluripotent cell lines.
    Cell. 2011 Feb 4;144(3):439-52 PMID: 21295703
  9. The LMO2 T-cell oncogene is activated via chromosomal translocations or retroviral insertion during gene therapy but has no mandatory role in normal T-cell development.
    Mol Cell Biol. 2003 Dec;23(24):9003-13 PMID: 14645513
  10. DNA methyltransferase 1 is essential for and uniquely regulates hematopoietic stem and progenitor cells.
    Cell Stem Cell. 2009 Oct 2;5(4):442-9 PMID: 19796624
  11. DNA-binding factors shape the mouse methylome at distal regulatory regions.
    Nature. 2011 Dec 14;480(7378):490-5 PMID: 22170606
  12. High GATA-2 expression inhibits human hematopoietic stem and progenitor cell function by effects on cell cycle.
    Blood. 2009 Mar 19;113(12):2661-72 PMID: 19168794
  13. DNA methylation patterns and epigenetic memory.
    Genes Dev. 2002 Jan 1;16(1):6-21 PMID: 11782440
  14. Ligand targeting of EphA2 enhances keratinocyte adhesion and differentiation via desmoglein 1.
    Mol Biol Cell. 2010 Nov 15;21(22):3902-14 PMID: 20861311
  15. Purification and characterization of mouse hematopoietic stem cells.
    Science. 1988 Jul 1;241(4861):58-62 PMID: 2898810
  16. A unique regulatory phase of DNA methylation in the early mammalian embryo.
    Nature. 2012 Mar 28;484(7394):339-44 PMID: 22456710
  17. Transcriptional competence and the active marking of tissue-specific enhancers by defined transcription factors in embryonic and induced pluripotent stem cells.
    Genes Dev. 2009 Dec 15;23(24):2824-38 PMID: 20008934
  18. DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction.
    Nat Genet. 2009 Nov;41(11):1207-15 PMID: 19801979
  19. Runx1 modulates developmental, but not injury-driven, hair follicle stem cell activation.
    Development. 2008 Mar;135(6):1059-68 PMID: 18256199
  20. Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential a revised road map for adult blood lineage commitment.
    Cell. 2005 Apr 22;121(2):295-306 PMID: 15851035
  21. A compendium of genome-wide hematopoietic transcription factor maps supports the identification of gene regulatory control mechanisms.
    Exp Hematol. 2011 May;39(5):531-41 PMID: 21338655
  22. The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores.
    Nat Genet. 2009 Feb;41(2):178-186 PMID: 19151715
  23. Quantitative comparison of genome-wide DNA methylation mapping technologies.
    Nat Biotechnol. 2010 Oct;28(10):1106-14 PMID: 20852634
  24. Ectopic expression of TAL-1 protein in Ly-6E.1-htal-1 transgenic mice induces defects in B- and T-lymphoid differentiation.
    Blood. 2002 Jul 15;100(2):491-500 PMID: 12091340
  25. Epigenetic dynamics of stem cells and cell lineage commitment: digging Waddington's canal.
    Nat Rev Mol Cell Biol. 2009 Aug;10(8):526-37 PMID: 19603040
  26. Densely interconnected transcriptional circuits control cell states in human hematopoiesis.
    Cell. 2011 Jan 21;144(2):296-309 PMID: 21241896
  27. Preparation of reduced representation bisulfite sequencing libraries for genome-scale DNA methylation profiling.
    Nat Protoc. 2011 Apr;6(4):468-81 PMID: 21412275
  28. Human DNA methylomes at base resolution show widespread epigenomic differences.
    Nature. 2009 Nov 19;462(7271):315-22 PMID: 19829295
  29. Comprehensive methylome map of lineage commitment from haematopoietic progenitors.
    Nature. 2010 Sep 16;467(7313):338-42 PMID: 20720541
  30. Hematopoietic fingerprints: an expression database of stem cells and their progeny.
    Cell Stem Cell. 2007 Nov;1(5):578-91 PMID: 18371395
  31. Loss of HOXC6 expression induces apoptosis in prostate cancer cells.
    Oncogene. 2005 Jan 6;24(1):188-98 PMID: 15637592
  32. Genome-wide maps of histone modifications unwind in vivo chromatin states of the hair follicle lineage.
    Cell Stem Cell. 2011 Sep 2;9(3):219-32 PMID: 21885018
  33. Global DNA demethylation during mouse erythropoiesis in vivo.
    Science. 2011 Nov 11;334(6057):799-802 PMID: 22076376
  34. Hair follicle stem cells are specified and function in early skin morphogenesis.
    Cell Stem Cell. 2008 Jul 3;3(1):33-43 PMID: 18593557
  35. Use of gene-expression profiling to identify prognostic subclasses in adult acute myeloid leukemia.
    N Engl J Med. 2004 Apr 15;350(16):1605-16 PMID: 15084693
Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-4164
DOI
10.1016/j.molcel.2012.06.019
Published
2012-08-24
Epub
2012-00-26
Pages
633-47
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC3428428
Subset
IM
Grants
NIAMS NIH HHS · R01 AR031737 · United States
NIAMS NIH HHS · R01AR31737 · United States
Databases
GEO
GSE38557
External Links
PubMed source DOI: 10.1016/j.molcel.2012.06.019 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2