A Runx1 Intronic Enhancer Marks Hemogenic Endothelial Cells and Hematopoietic Stem Cells§

Authors


  • Author contributions: C.E.L.N.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing; T.Y.: collection and assembly of data, data analysis and interpretation; N.Y.: collection and assembly of data; B.C.: collection of data; H.J.: provision of study material; Z.W.: provision of study material; Y.I.: manuscript writing, financial support; M.O.: conception and design, financial support, collection and assembly of data, data analysis and interpretation, manuscript writing.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLS EXPRESS August 26, 2010.

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. STEM CELLS 2010;28:1869–1881

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