A Runx1 intronic enhancer marks hemogenic endothelial cells and hematopoietic stem cells.
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 Runx1 gene expression remain to be elucidated. Herewith, we report the identification of an intronic Runx1 enhancer, Runx1 +24 mouse conserved noncoding element (mCNE), using a combinatorial in silico approach 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 novo generation 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.
Ng
Cherry Ee Lin
CE
Cancer Science Institute of Singapore, National University of Singapore, Singapore.
Yokomizo
Tomomasa
T
Yamashita
Namiko
N
Cirovic
Branko
B
Jin
Hao
H
Wen
Zilong
Z
Ito
Yoshiaki
Y
Osato
Motomi
M
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D055018:Hemangioblasts / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data
D050676:Core Binding Factor Alpha 2 Subunit