DNA methyltransferase 1 is essential for and uniquely regulates hematopoietic stem and progenitor cells.
Document Type
Article
Publication Date
10-2-2009
Keywords
Animals, Blotting, Western, Bone Marrow Transplantation, DNA (Cytosine-5-)-Methyltransferase, Female, Flow Cytometry, Hematopoietic Stem Cells, Mice, Polymerase Chain Reaction
Volume
5
Issue
4
First Page
442
Last Page
449
ISSN
1875-9777
JAX Source
Cell Stem Cell 2009 Oct 2; 5(4):442-9.
PMID
19796624
Abstract
DNA methylation is essential for development and in diverse biological processes. The DNA methyltransferase Dnmt1 maintains parental cell methylation patterns on daughter DNA strands in mitotic cells; however, the precise role of Dnmt1 in regulation of quiescent adult stem cells is not known. To examine the role of Dnmt1 in adult hematopoietic stem cells (HSCs), we conditionally disrupted Dnmt1 in the hematopoietic system. Defects were observed in Dnmt1-deficient HSC self-renewal, niche retention, and in the ability of Dnmt1-deficient HSCs to give rise to multilineage hematopoiesis. Loss of Dnmt1 also had specific impact on myeloid progenitor cells, causing enhanced cell cycling and inappropriate expression of mature lineage genes. Dnmt1 regulates distinct patterns of methylation and expression of discrete gene families in long-term HSCs and multipotent and lineage-restricted progenitors, suggesting that Dnmt1 differentially controls these populations. These findings establish a unique and critical role for Dnmt1 in the primitive hematopoietic compartment.
Recommended Citation
Trowbridge JJ,
Snow J,
Kim J,
Orkin S.
DNA methyltransferase 1 is essential for and uniquely regulates hematopoietic stem and progenitor cells. Cell Stem Cell 2009 Oct 2; 5(4):442-9.