| Autor: |
Ng, Cherry Ee Lin, Yokomizo, Tomomasa, Yamashita, Namiko, Cirovic, Branko, Jin, Hao, Wen, Zilong, Ito, Yoshiaki, Osato, Motomi |
| Zdroj: |
Stem Cells; October 2010, Vol. 28 Issue: 10 p1869-1881, 13p |
| Abstrakt: |
Runx1 is essential for the generation of hematopoietic stem cells (HSCs) and is frequently mutated in human leukemias. However, the cis‐regulatory mechanisms modulating the Runx1gene expression remain to be elucidated. Herewith, we report the identification of an intronic Runx1enhancer, Runx1+24 mouse conserved noncoding element (mCNE), using a combinatorial in silicoapproach involving comparative genomics and retroviral integration sites mapping. The Runx1+24 mCNE was found to possess hematopoietic‐specific enhancer activity in both zebrafish and mouse models. Significantly, this enhancer is active specifically in hemogenic endothelial cells (ECs) at sites where the de novogeneration of HSCs occurs. The activity of this enhancer is also strictly restricted to HSCs within the hematopoietic compartment of the adult bone marrow. We anticipate that Runx1+24 mCNE HSC enhancer will serve as a molecular handle for tracing and/or manipulating hemogenic ECs/HSCs behavior in vivo, and consequently become an invaluable tool for research on stem cell and cancer biology. STEMCELLS2010;28:1869–1881 |
| Databáze: |
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