title: A Runx1 intronic enhancer marks hemogenic endothelial cells and hematopoietic stem cells.
abstract: 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.
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors.forename: Cherry Ee Lin
authors.initials: CE
authors.lastname: Ng
authors.forename: Tomomasa
authors.initials: T
authors.lastname: Yokomizo
authors.forename: Namiko
authors.initials: N
authors.lastname: Yamashita
authors.forename: Branko
authors.initials: B
authors.lastname: Cirovic
authors.forename: Hao
authors.initials: H
authors.lastname: Jin
authors.forename: Zilong
authors.initials: Z
authors.lastname: Wen
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ito
authors.forename: Motomi
authors.initials: M
authors.lastname: Osato
mesh_terms: 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
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit