Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.37 (DNA methyltransferase)
 4,983 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hematopoietic stem cells (HSCs) are widely used in transplantation therapy to treat a variety of blood diseases. The success of hematopoietic recovery is of high importance and closely related to the patient's morbidity and mortality after Hematopoietic stem cell transplantation (HSCT). We have previously shown that SALL4 is a potent stimulator for the expansion of human hematopoietic stem/progenitor cells in vitro. In these studies, we demonstrated that systemic administration with TAT-SALL4B resulted in expediting auto-reconstitution and inducing a 30-fold expansion of endogenous HSCs/HPCs in mice exposed to a high dose of irradiation. Most importantly, TAT-SALL4B treatment markedly prevented death in mice receiving lethal irradiation. Our studies also showed that TAT-SALL4B treatment was able to enhance both the short-term and long-term engraftment of human cord blood (CB) cells in NOD/SCID mice and the mechanism was likely related to the in vivo expansion of donor cells in a recipient. This robust expansion was required for the association of SALL4B with DNA methyltransferase complex, an epigenetic regulator critical in maintaining HSC pools and in normal lineage progression. Our results may provide a useful strategy to enhance hematopoietic recovery and reconstitution in cord blood transplantation with a recombinant TAT-SALL4B fusion protein.
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PMID:Enhancing bone marrow regeneration by SALL4 protein. 2428 61

The ability of adult stem cells to reside in a quiescent state is crucial for preventing premature exhaustion of the stem cell pool. However, the intrinsic epigenetic factors that regulate spermatogonial stem cell quiescence are largely unknown. Here, we investigate in mice how DNA methyltransferase 3-like (DNMT3L), an epigenetic regulator important for interpreting chromatin context and facilitating de novo DNA methylation, sustains the long-term male germ cell pool. We demonstrated that stem cell-enriched THY1(+) spermatogonial stem/progenitor cells (SPCs) constituted a DNMT3L-expressing population in postnatal testes. DNMT3L influenced the stability of promyelocytic leukemia zinc finger (PLZF), potentially by downregulating Cdk2/CDK2 expression, which sequestered CDK2-mediated PLZF degradation. Reduced PLZF in Dnmt3l KO THY1(+) cells released its antagonist, Sal-like protein 4A (SALL4A), which is associated with overactivated ERK and AKT signaling cascades. Furthermore, DNMT3L was required to suppress the cell proliferation-promoting factor SALL4B in THY1(+) SPCs and to prevent premature stem cell exhaustion. Our results indicate that DNMT3L is required to delicately balance the cycling and quiescence of SPCs. These findings reveal a novel role for DNMT3L in modulating postnatal SPC cell fate decisions.
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PMID:DNMT3L promotes quiescence in postnatal spermatogonial progenitor cells. 2485 Aug 56